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1.
Behav Res Methods ; 56(4): 3861-3872, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38332413

ABSTRACT

Over the last 40 years, object recognition studies have moved from using simple line drawings, to more detailed illustrations, to more ecologically valid photographic representations. Researchers now have access to various stimuli sets, however, existing sets lack the ability to independently manipulate item format, as the concepts depicted are unique to the set they derive from. To enable such comparisons, Rossion and Pourtois (2004) revisited Snodgrass and Vanderwart's (1980) line drawings and digitally re-drew the objects, adding texture and shading. In the current study, we took this further and created a set of stimuli that showcase the same objects in photographic form. We selected six photographs of each object (three color/three grayscale) and collected normative data and RTs. Naming accuracy and agreement was high for all photographs and appeared to steadily increase with format distinctiveness. In contrast to previous data patterns for drawings, naming agreement (H values) did not differ between grey and color photographs, nor did familiarity ratings. However, grey photographs received significantly lower mental imagery agreement and visual complexity scores than color photographs. This suggests that, in comparison to drawings, the ecological nature of photographs may facilitate deeper critical evaluation of whether they offer a good match to a mental representation. Color may therefore play a more vital role in photographs than in drawings, aiding participants in judging the match with their mental representation. This new photographic stimulus set and corresponding normative data provide valuable materials for a wide range of experimental studies of object recognition.


Subject(s)
Pattern Recognition, Visual , Photic Stimulation , Photography , Recognition, Psychology , Humans , Male , Female , Photography/methods , Recognition, Psychology/physiology , Pattern Recognition, Visual/physiology , Adult , Reaction Time/physiology , Young Adult , Adolescent
2.
Memory ; 31(7): 905-917, 2023 08.
Article in English | MEDLINE | ID: mdl-37165509

ABSTRACT

ABSTRACTWe report three experiments designed to reveal the mechanisms that underlie subjective experiences of recognition by examining effects of how those experiences are measured. Prior research has explored the potential influences of collecting metacognitive measures on memory performance. Building on this work, here we systematically evaluated whether cross-measure contamination occurs when remember-know (RK) and/or confidence (C) judgments are made after old/new recognition decisions. In Experiment 1, making either RK or C judgments did not significantly influence recognition relative to a standard no-judgment condition. In Experiment 2, making RK judgments in addition to C judgments did not significantly affect recognition or confidence. In Experiment 3, making C judgments in addition to RK judgments did not significantly affect recognition or patterns of RK responses. Cross-contamination was not apparent regardless of whether items were studied using a shallow or deep levels-of-processing task - a manipulation that yielded robust effects on recognition, RK judgments, and C. Our results indicate that under some conditions, participants can independently evaluate their recognition, subjective recognition experience, and confidence. Though contamination across measures of metamemory and memory is always possible, it may not be inevitable. This has implications for the mechanisms that underlie subjective experiences that accompany recognition judgments.


Subject(s)
Mental Recall , Metacognition , Humans , Mental Recall/physiology , Recognition, Psychology/physiology , Judgment/physiology , Cognition
3.
PLoS One ; 14(9): e0222644, 2019.
Article in English | MEDLINE | ID: mdl-31513687

ABSTRACT

[This corrects the article DOI: 10.1371/journal.pone.0220526.].

4.
PLoS One ; 14(7): e0220526, 2019.
Article in English | MEDLINE | ID: mdl-31365587

ABSTRACT

Previous work supports an age-specific impairment for recognition memory of pairs of words and other stimuli. The present study tested the generalization of an associative deficit across word, name, and nonword stimulus types in younger and older adults. Participants completed associative and item memory tests in one of three stimulus conditions and made metacognitive ratings of perceptions of self-efficacy, task success ("postdictions"), strategy success, task effort, difficulty, fatigue, and stamina. Surprisingly, no support was found for an age-related associative deficit on any of the stimulus types. We analyzed our data further using a multilayer perceptron artificial neural network. The network was trained to classify individuals as younger or older and its hidden unit activities were examined to identify data patterns that distinguished younger from older participants. Analysis of hidden unit activities revealed that the network was able to correctly classify by identifying three different clusters of participants, with two qualitatively different groups of older individuals. One cluster of older individuals found the tasks to be relatively easy, they believed they had performed well, and their beliefs were accurate. The other cluster of older individuals found the tasks to be difficult, believed they were performing relatively poorly, yet their beliefs did not map accurately onto their performance. Crucially, data from the associative task were more useful for neural networks to discriminate between younger and older adults than data from the item task. This work underscores the importance of considering both individual and age differences as well as metacognitive responses in the context of associative memory paradigms.


Subject(s)
Association Learning , Individuality , Memory Disorders/physiopathology , Memory/physiology , Metacognition/physiology , Neural Networks, Computer , Recognition, Psychology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Young Adult
5.
Mem Cognit ; 47(7): 1359-1374, 2019 10.
Article in English | MEDLINE | ID: mdl-31119498

ABSTRACT

In the remember/know paradigm, a "know" response can be defined to participants as a high-confidence state of certainty or as a low-confidence state based on a feeling of familiarity. To examine the effects of definition on use of responses, in two experiments, definitions of "remember" and "guess" were kept constant, but definitions of "know" and/or "familiar" were systematically varied to emphasize (a) a subjective experience of high confidence without recollection, (b) a feeling of familiarity, (c) both of these subjective experiences combined within one response option, or (d) both of these experiences as separate response options. The confidence expressed in "know" and/or "familiar" definitions affected how participants used response options. Importantly, this included use of the "remember" response, which tended to be used more frequently when the nonrecollection-based middle response option emphasized a feeling of familiarity rather than an experience of "just knowing." The influence of the definitions on response patterns was greater for items that had undergone deep rather than shallow processing, and was greater when deep-encoded and shallow-encoded items were mixed, rather than blocked, at test. Our findings fit with previous research suggesting that the mnemonic traces underlying subjective judgments are continuous and that the remember/know paradigm is not a pure measure of underlying processes. Findings also emphasize the importance of researchers publishing the exact definitions they have used to enable accurate comparisons across studies.


Subject(s)
Judgment , Mental Recall , Recognition, Psychology , Adolescent , Adult , Aged , Attention , Culture , Female , Humans , Male , Middle Aged , Retention, Psychology , Verbal Learning , Young Adult
6.
Can J Exp Psychol ; 73(2): 94-99, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30802078

ABSTRACT

Independent recollection-familiarity (RF) ratings are sometimes collected to measure subjective experiences of recollection and familiarity during recognition. Although the RF ratings task purports to measure the degree to which each recognition state is experienced, the rating scale has been worded in terms of confidence rather than amount. Given prior evidence that wording influences recognition and remember/know judgments, we compared RF rating scales worded in terms of amount versus confidence across 2 groups. A robust levels-of-processing effect occurred on both recollection and familiarity ratings, and its magnitude was similar across scale wording. Scale wording did not influence recognition, and, most importantly, it had little influence on ratings of recollection and familiarity. These findings suggest that participants may use confidence to rate amount, or vice versa. Regardless, researchers should align their task instructions and scale wording, and should publish them. Such alignment and transparency is crucial for interpreting measures of the memory states that arise during recognition memory. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Subject(s)
Mental Recall/physiology , Metacognition/physiology , Psychometrics/instrumentation , Recognition, Psychology/physiology , Adolescent , Adult , Female , Humans , Male , Psychometrics/standards , Young Adult
7.
Exp Aging Res ; 41(2): 157-76, 2015.
Article in English | MEDLINE | ID: mdl-25724014

ABSTRACT

UNLABELLED: BACKGROUND/STUDY CONTEXT: Older adults have more complex and differentiated views of aging than do younger adults, but less is known about age-related perceptions of Alzheimer's disease. This study investigated age-related perceptions of competence of an older adult labeled as "in good health" (healthy) or "has Alzheimer's disease" (AD), using a person-perception paradigm. It was predicted that older adults would provide more differentiated assessments of the two targets than would younger adults. METHODS: Younger (n=86; 18-36 years) and older (n=66; 61-95 years) adults rated activities of daily living (ADL), instrumental activities of daily living (IADL), and memory abilities of a female target aged 75 years, described as healthy or with AD. Data on anxiety about aging, knowledge of and experience with aging and AD, knowledge of memory aging, and positive and negative biases toward aging and AD were also collected. RESULTS: Older adults perceived the healthy target as more capable of cognitively effortful activities (e.g., managing finances) and as possessing better memory abilities than the AD target. As predicted, these differences were greater than differences between targets perceived by younger adults. The interaction effect remained significant after statistically controlling for relevant variables, including education and gender. Additionally, exploratory analyses revealed that older adults held less positively biased views of AD than younger adults, but negatively biased views were equivalent between age groups. CONCLUSION: The results demonstrate that mere labels of "healthy" and "Alzheimer's disease" produce significant and subtle age differences in perceived competencies of older adults, and that biases towards AD vary by age group and valence. Our findings extend the person-perception paradigm to an integrative analysis of aging and AD, are consistent with models of adult development, and complement current research and theory on stereotypes of aging. Future directions for research on perceptions of aging are suggested.


Subject(s)
Aging/psychology , Alzheimer Disease/psychology , Perception , Activities of Daily Living , Adolescent , Adult , Aged , Aged, 80 and over , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Memory , Middle Aged , Young Adult
8.
Memory ; 23(7): 981-90, 2015.
Article in English | MEDLINE | ID: mdl-25142025

ABSTRACT

In the Remember-Know paradigm whether a Know response is defined as a high-confidence state of certainty or a low-confidence state based on familiarity varies across researchers and can influence participants' responses. The current experiment was designed to explore differences between the states of Know and Familiar. Participants studied others' justification statements to "Know" recognition decisions and separated them into two types. Crucially, participants were not provided definitions of Know and Familiar on which to sort the items--their judgements were based solely on the phenomenology described in the justifications. Participants' sorting decisions were shown to reliably map onto expert classification of Know and Familiar. Post-task questionnaire responses demonstrated that both the level of memory detail and confidence expressed in the justifications were central to how participants categorised the items. In sum, given no instructions to do so, participants classify Familiar and Know according to two dimensions: confidence and amount of information retrieved.


Subject(s)
Awareness , Decision Making , Judgment , Mental Recall , Recognition, Psychology , Adolescent , Adult , Cues , Female , Humans , Male , Retention, Psychology , Surveys and Questionnaires , Young Adult
9.
Pharmaceuticals (Basel) ; 6(4): 469-79, 2013 Mar 26.
Article in English | MEDLINE | ID: mdl-24276118

ABSTRACT

Stimulation of the dopamine D1 receptor is reported to cause the phosphorylation of DARPP-32 at the thre34 position and activates the protein. If intracellular Ca2+ is increased, such as after activation of the glutamate NMDA receptor, calcineurin activity increases and the phosphates will be removed. This balance of phosphorylation control suggests that a D1 receptor agonist and a NMDA glutamate receptor antagonist should have additive or synergistic actions to increase activated DARPP-32 and consequent behavioral effects. This hypothesis was tested in a volitional consumption of ethanol model: the selectively bred Myers' high ethanol preferring (mHEP) rat. A 3-day baseline period was followed by 3-days of twice daily injections of drug(s) or vehicle(s) and then a 3-day post-treatment period. Vehicle, the D1 agonist SKF 38393, the non-competitive NMDA receptor antagonist memantine, or their combination were injected 2 h before and after lights out. The combination of 5.0 mg/kg SKF 38393 with either 3.0 or 10 mg/kg memantine did not produce an additive or synergistic effect. For example, 5.0 mg/kg SKF reduced consumption of ethanol by 27.3% and 10 mg/kg memantine by 39.8%. When combined, consumption declined by 48.2% and the proportion of ethanol solution to total fluids consumed declined by 17%. However, the consumption of food also declined by 36.6%. The latter result indicates that this dose combination had a non-specific effect. The combination of SKF 38393 with (+)-MK-801, another NMDA receptor antagonist, also failed to show an additive effect. The lack of additivity and specificity suggests that the hypothesis may not be correct for this in vivo model.  The interaction of these different receptor systems with intraneuronal signaling and behaviors needs to be studied further.

10.
Conscious Cogn ; 22(2): 572-88, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23619311

ABSTRACT

The Remember-Know paradigm is commonly used to examine experiential states during recognition. In this paradigm, whether a Know response is defined as a high-confidence state of certainty or a low-confidence state based on familiarity varies across researchers, and differences in definitions and instructions have been shown to influence participants' responding. Using a novel approach, in three internet-based questionnaires participants were placed in the role of 'memory expert' and classified others' justifications of recognition decisions. Results demonstrated that participants reliably differentiated between others' memory experiences--both in terms of confidence and other inherent differences in the justifications. Furthermore, under certain conditions, manipulations of confidence were found to shift how items were assigned to subjective experience categories (Remember, Know, Familiar, and Guess). Findings are discussed in relation to the relationship between subjective experience and confidence, and the separation of Know and Familiar response categories within the Remember-Know paradigm.


Subject(s)
Judgment , Recognition, Psychology/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Imagination/physiology , Male , Middle Aged , Young Adult
11.
Article in English | MEDLINE | ID: mdl-23367874

ABSTRACT

Older adults have considerable impairment in associative recognition despite minimal age differences in item recognition. The magnitude of this associative deficit varies by type of stimuli, strategy utilization, and other mediators and moderators ( Old & Naveh-Benjamin, 2008 , Psychology and Aging, 23, 104-118). Name pair stimuli have not been used to test the associative deficit hypothesis (ADH), although tests using name-face stimuli support the ADH. Additionally, metacognitive awareness of the ADH has not been investigated. We tested the ADH with word and name pair stimuli, and predicted that age-related associative deficits would be larger for words than names because names, unlike most common nouns, lack certain semantic properties that could be used to bind pairs of names together. Results supported the ADH for words but not names: Younger and older adults recognized equivalently fewer names on the associative test relative to the item test. As predicted, self-efficacy was higher for younger than older adults. Surprisingly, self-efficacy for the associative test was higher than for the item test but post-test estimates of performance success (postdictions) were higher for the item test than for the associative test, suggesting sensitivity by participants to different task demands in the item and associative tests following recognition attempts. Metacognitive accuracy was better for words than names and for the item test than associative test, and equivalent between age groups. Overall, participants overestimated their name recognition abilities. Our findings extend support for the ADH to a conceptually important and ecologically valid domain (names) and provide new data on metacognitive aspects of the ADH.


Subject(s)
Aging , Association , Awareness , Cognition , Recognition, Psychology , Adolescent , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Self Efficacy , Word Association Tests , Young Adult
12.
Cortex ; 49(6): 1598-609, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23107379

ABSTRACT

INTRODUCTION: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder primarily affecting social interaction and communication. Recently, there has been interest in whether people with ASD also show memory deficits as a result of abnormal brain development. However, at least in adolescents with ASD, the recollection component of episodic memory has rarely been explored. This paper is an evaluation of recollection in three different experiments in adolescents with ASD, using both objective (source discrimination) and subjective methods (Remember-Know judgments). METHODS: Three experiments were designed to measure different aspects of contextual information: sensory/perceptual information (Experiment 1), temporal information (Experiment 2) and spatial information (Experiment 3). To measure objective and subjective recollection, for all three experiments, all participants were presented with information to learn in a specific context. At the recognition stage, they were asked whether they remembered the information or just knew the information was there (R/K response, subjective method). To assess the quality of these subjective judgments, participants justified their Remember responses using the contextual information. After the recognition task, to assess source memory (objective measure), all items presented at encoding were represented and participants have to recall the source for all these items. RESULTS: All three experiments showed that adolescents with ASD could correctly recall source information. However, in the first experiment adolescents with ASD gave significantly fewer Remember responses than controls. CONCLUSIONS: These findings point to a specific and subtle recollection impairment in adolescents with ASD, at least when subjective methods are used. We discuss how these might relate to differences in the self and to the brain abnormalities in ASD.


Subject(s)
Child Development Disorders, Pervasive/psychology , Mental Recall/physiology , Adolescent , Analysis of Variance , Discrimination, Psychological/physiology , Female , Humans , Intelligence Tests , Judgment , Male , Memory/physiology , Mental Processes , Neuropsychological Tests , Perception/physiology , Photic Stimulation , Psychomotor Performance/physiology , Recognition, Psychology/physiology , Sensation/physiology , Space Perception/physiology
13.
Basic Clin Pharmacol Toxicol ; 106(5): 435-44, 2010 May.
Article in English | MEDLINE | ID: mdl-20210793

ABSTRACT

Potent N-methyl-d-aspartate (NMDA) receptor antagonists decrease volitional consumption of ethanol by rats. This study examined the effects of memantine, a low-affinity, open channel NMDA antagonist, on volitional consumption of ethanol by alcohol-preferring rats and potential locomotor, sedative and hypothermic effects. Volitional consumption of ethanol in a 24-hr two-choice paradigm was determined for male Myers' high-ethanol-preferring (mHEP) rats. Effects of memantine (0.3, 1.0, 3.0 and 10.0 mg/kg, i.p., b.i.d. [twice daily] for 3 days) or vehicle on volitional consumption of ethanol, proportion of ethanol to total fluids consumed, total fluid intake and consumption of food were observed. Potential sedating and locomotor effects of memantine (10.0 mg/kg, i.p., b.i.d.) were determined using an elevated plus maze and an Auto-Track Opto-Varimex activity monitoring system. Rectal temperature was measured to determine if memantine (10.0 mg/kg, i.p.) produces a hypothermic effect. The results indicate that memantine dose-dependently decreased the amount of ethanol and proportion of ethanol to total fluids consumed daily, reaching 48% and 24%, respectively, at the highest dose. These effects did not appear to be anti-caloric. Memantine (10.0 mg/kg) partially reversed both the sedation and the reductions in locomotor activity induced by ethanol. This dose did, however, produce a small, partially reversible hypothermic effect. In conclusion, memantine may decrease ethanol consumption with fewer side effects than other NMDA receptor antagonists, such as phencyclidine (PCP), MK 801 and ketamine.


Subject(s)
Alcoholism/drug therapy , Memantine/therapeutic use , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Animals , Ethanol/administration & dosage , Ethanol/adverse effects , Male , Motor Activity/drug effects , Rats , Rats, Wistar , Self Administration , Volition
14.
Alcohol Clin Exp Res ; 31(11): 1866-71, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17908267

ABSTRACT

BACKGROUND: Inhibitors of monoamine neurotransmitter transporters are well established as antidepressants. However, the evidence that single (serotonin) or dual (serotonin-norepinephrine) neurotransmitter uptake inhibitors can treat ethanol abuse, either as a comorbidity with depression or as a separate entity, is inconsistent. Drugs that have, in addition, the ability to inhibit dopamine uptake may have an advantage in the treatment of alcohol abuse. Therefore, the inhibitor of norepinephrine, serotonin and dopamine uptake, DOV 102,677, was tested for its effects on the volitional consumption of ethanol by an ethanol-preferring rat strain. METHODS: Myers' high ethanol-preferring rats were screened by a 10-day, 3 to 30% step-up test and then given free access to the preferred concentration of ethanol in a 3-bottle choice task. Consumption of ethanol (g/kg), water, food, and body weight were measured daily during a 3-day predrug treatment period, a 3-day treatment period, and a 3-day posttreatment period. Additional Sprague-Dawley rats were observed for 24 hours for the behavioral effects of 2.0 mg/kg s.c. reserpine after a 30-minute pretreatment with different doses of DOV 102,677. RESULTS: The triple monoamine uptake inhibitor DOV 102,677 dose-dependently decreased the volitional consumption of ethanol by as much as 71.2% (20 mg/kg i.p., b.i.d.) over 3 days of administration. This effect carried over into the posttreatment period. Similarly, the proportion of ethanol to total fluids consumed declined by 66.2% (20 mg/kg s.c., b.i.d.), while food consumption and body weight were unaltered. In contrast, amperozide (2 mg/kg i.p., b.i.d.) suppressed the amount of ethanol consumed by 56%, while naltrexone (5 mg/kg i.p., b.i.d.) was without effect. DOV 102,677 (40 mg/kg s.c.) inhibited reserpine-induced akinesia and ptosis, but not hypothermia in Sprague-Dawley rats, consistent with its transient inhibition of serotonin transport, and more long-lived inhibition of norepinephrine and dopamine uptake. CONCLUSIONS: DOV 102,677 significantly decreased the volitional consumption of ethanol with minimal alterations in the intake of food or on body weight in an ethanol-preferring rat strain, suggesting that triple reuptake inhibitors may find utility in treating alcohol abuse.


Subject(s)
Alcohol Drinking/genetics , Alcohol Drinking/physiopathology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacology , Adrenergic Uptake Inhibitors/pharmacology , Animals , Behavior, Animal/drug effects , Body Weight/drug effects , Dose-Response Relationship, Drug , Drug Interactions , Eating/drug effects , Female , Male , Rats , Rats, Inbred Strains , Rats, Sprague-Dawley , Reserpine/pharmacology
15.
Neurotoxicol Teratol ; 29(1): 31-6, 2007.
Article in English | MEDLINE | ID: mdl-17097852

ABSTRACT

Epidemiologic studies establish a relationship between nicotine use by adolescents and a subsequent involvement with drugs of abuse in adulthood. Recent research implicates the periadolescent period as a crucial time in development, during which nicotine use produces persistent adaptations that serve to predispose an individual to substance use. The present investigation evaluated the effects of periadolescent nicotine priming on young adult sensitization to reinforcement by a drug of abuse. Nicotine (0.4 mg/kg, intraperitoneal), mecamylamine (2 mg/kg, subcutaneous), mecamylamine and nicotine, or saline was administered as a once-daily injection to periadolescent (postnatal days 35-44) Sprague-Dawley male rats. The effects of periadolescent nicotine priming on reinforcement parameters in the young adult animal (postnatal day 80) were measured by conditioning a place preference with diazepam (1 mg/kg, subcutaneous). Rats were tested for place conditioning in a drug-free state. In contrast to other periadolescent treatment groups, rats treated with only nicotine during periadolescence showed a heterologous sensitization to the subthreshold dose of diazepam utilized during conditioning. Pretreatment with mecamylamine before periadolescent nicotine priming prevented the enhanced response to diazepam observed in the young adult animal. Priming with nicotine during late adolescence (postnatal days 60-69) failed to sensitize the adult rats to diazepam. This study supports a relationship between periadolescent nicotine priming and the production of persistent, behavioral adaptations in the young adult animal.


Subject(s)
Anti-Anxiety Agents/pharmacology , Conditioning, Operant/drug effects , Diazepam/pharmacology , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Reinforcement, Psychology , Age Factors , Animals , Behavior, Animal/drug effects , Drug Interactions , Male , Rats , Rats, Sprague-Dawley
16.
Basic Clin Pharmacol Toxicol ; 99(5): 340-5, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17076684

ABSTRACT

Literature has reported a controversy concerning the effects of the environmental pollutant perchlorate on pertinent physiological systems. However, no research to date has evaluated the effect of concomitant consumption of perchlorate and an additional environmental contaminant on physiological systems. The present preliminary investigation served to assess the effects of oral consumption of perchlorate, alone and in combination with ethanol, on thyroid hormone and brain catecholamine concentrations in female rats of gestational age. Forty, female Myers' high ethanol-preferring rats were randomly assigned to 1 of 7 groups that received: (1) deionized water, both bottles (2) deionized water and 10% ethanol (v/v), two separate bottles (3) 300 microg/l perchlorate solution in deionized water, both bottles (4) 300 microg/l perchlorate in deionized water and in 10% ethanol (v/v), two separate bottles (5) 3000 microg/l perchlorate solution in deionized water, both bottles (6) 3000 microg/l perchlorate in deionized water and in 10% ethanol (v/v), two separate bottles (7) 0.01% propylthiouracil solution in deionized water, both bottles. At cessation of the treatment period, plasma triiodothyronine (T3) and thyroxine (T4) levels were measured by radioimmunoassay and brain area concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine were measured by high performance liquid chromatography. Perchlorate consumption, alone and/or in combination with ethanol consumption, failed to produce significant alterations from control values for triiodothyronine, thyroxine, dopamine, DOPAC, or norepinephrine. The data suggest that the no-observed effect level of perchlorate consumption on thyroid hormone and brain catecholamine concentrations is above the 3000 microg/l concentration in the adult female rat.


Subject(s)
Alcohol-Induced Disorders, Nervous System/blood , Brain/drug effects , Catecholamines/metabolism , Environmental Pollutants/toxicity , Ethanol/toxicity , Perchlorates/toxicity , Thyroid Hormones/blood , Animals , Animals, Outbred Strains , Brain/metabolism , Brain Chemistry , Catecholamines/analysis , Chromatography, High Pressure Liquid , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Combinations , Female , Propylthiouracil/pharmacology , Rats
17.
Alcohol Alcohol ; 40(6): 494-7, 2005.
Article in English | MEDLINE | ID: mdl-16186143

ABSTRACT

AIMS: To compare the effect of an antagonist of the mGlu5 glutamate receptor, 2-methyl-6-(phenylethynyl)pyridine (MPEP) on a test for anxiety and on the volitional consumption of ethanol. METHODS: The test for anxiety was placement of a Sprague-Dawley rat for a 5 min observation period in an elevated plus-maze. Volitional consumption of ethanol in a two-choice paradigm was determined for male and female myers high ethanol-preferring rats after a 10-day 'step-up' test of 3-30% v/v ethanol vs water used to determine each rat's preferred concentration of ethanol. Each rat received a 4-day baseline period, 3-days of drug injection b.i.d., and a 4-day post-treatment period and then rotated to a different dose of drug or vehicle. RESULTS: The effects of MPEP on elevated plus-maze activity were not significant at doses up to 3.0 mg/kg subcutaneously 60 min. before observation. There was a dose-dependent, 0.3, 1.0, 3.0 mg/kg, decrease in consumption of preferred concentrations of ethanol, along with a decrease in the proportion of ethanol consumed to total fluids consumed. The 3.0 mg/kg b.i.d. dose of MPEP reduced consumption by 57%, proportion by 45%, and food intake by 10%. CONCLUSIONS: MPEP did not appear to have an anti-anxiety effect, but volitional drinking in a genetic model was reduced. The mGlu5 receptor may provide a target for drug action to reduce the consumption of ethanol.


Subject(s)
Alcohol Deterrents/pharmacology , Alcohol Drinking/genetics , Anti-Anxiety Agents/pharmacology , Arousal/drug effects , Fear/drug effects , Maze Learning/drug effects , Pyridines/pharmacology , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Animals , Arousal/genetics , Dose-Response Relationship, Drug , Eating/drug effects , Ethanol/administration & dosage , Female , Genotype , Injections, Intraperitoneal , Injections, Subcutaneous , Male , Rats , Rats, Inbred Strains , Rats, Sprague-Dawley , Rats, Wistar , Receptor, Metabotropic Glutamate 5
18.
Eur J Pharmacol ; 509(2-3): 161-4, 2005 Feb 21.
Article in English | MEDLINE | ID: mdl-15733551

ABSTRACT

There is increasing concern that abuse of tobacco during periadolescence increases the potential for later abuse of other drugs. To test this hypothesis, Sprague-Dawley rats received once-daily injections of either water or 0.4 mg/kg nicotine from postnatal day 35 through 44. Beginning on postnatal day 80, animals were tested in a 12-day cocaine-induced conditioned place preference (CPP) paradigm. Prior nicotine treatment enhanced the dose-response to cocaine. CPP training with 3.0 mg/kg i.p. cocaine increased time in drug-paired chambers by 50% in control rats and 94% in nicotine-exposed animals. Thus, periadolescent nicotine exposure produced long-term sensitization to an indirect-acting dopamine agonist.


Subject(s)
Cocaine/pharmacology , Nicotine/pharmacology , Reinforcement, Psychology , Analysis of Variance , Animals , Cocaine/administration & dosage , Conditioning, Operant/drug effects , Dose-Response Relationship, Drug , Male , Motor Activity/drug effects , Nicotine/administration & dosage , Rats , Rats, Sprague-Dawley , Time Factors
19.
Brain Res Bull ; 64(3): 279-84, 2004 Sep 30.
Article in English | MEDLINE | ID: mdl-15464866

ABSTRACT

The ability of drugs that reduce NMDA receptor activity on the volitional consumption of ethanol in the genetic drinking rat, mHEP line, was investigated. After the consumption of ethanol solutions and water by each male or female mHEP rat had stabilized on its preferred concentration, different doses of LY 274614, a competitive NMDA antagonist, MK 801, a non-competitive NMDA antagonist, (+)-HA-966 or ACPC (1-aminocyclopropane-1-carboxylic acid), antagonists of the glycine site were administered daily for three days. The dose of 3.0 mg/kg i.p. LY 274614 reduced the consumption of ethanol by 64% compared to the pre-treatment baseline, while 0.3 mg/kg of MK 801 reduced consumption by 44%, 20 mg/kg (+)-HA-966 reduced consumption by 47% and 300 mg/kg of ACPC reduced consumption by 30%. These doses of LY 274614 and MK 801 reduced the ability of Sprague-Dawley rats to walk on a rotorod. Effects of these drugs on food intake were small except for the 20 mg/kg dose of (+)-HA-966. Therefore, the drugs did not have an anti-caloric effect and manipulations of the glutamatergic system through NMDA receptors may modify the consumption of ethanol. This interaction should be explored further for its therapeutic potential and to better understand the control by central neuronal systems of the consumption of ethanol.


Subject(s)
Alcohol Drinking/drug therapy , Brain/drug effects , Ethanol/antagonists & inhibitors , Excitatory Amino Acid Antagonists/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Alcohol Drinking/genetics , Alcohol-Induced Disorders, Nervous System/drug therapy , Alcohol-Induced Disorders, Nervous System/genetics , Alcohol-Induced Disorders, Nervous System/physiopathology , Alcoholism/drug therapy , Alcoholism/genetics , Alcoholism/physiopathology , Amino Acids, Cyclic/pharmacology , Animals , Brain/metabolism , Brain/physiopathology , Disease Models, Animal , Dizocilpine Maleate/pharmacology , Dose-Response Relationship, Drug , Ethanol/adverse effects , Female , Genetic Predisposition to Disease , Glutamic Acid/metabolism , Isoquinolines/pharmacology , Male , Motor Activity/drug effects , Motor Activity/genetics , Pyrrolidinones/pharmacology , Rats , Rats, Inbred Strains , Rats, Sprague-Dawley , Receptors, Glycine/antagonists & inhibitors , Receptors, Glycine/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Volition/drug effects , Volition/physiology
20.
Naunyn Schmiedebergs Arch Pharmacol ; 366(4): 319-26, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12237745

ABSTRACT

It is hypothesized that although the overall metabolism of ethanol in the brain is very limited, a very small percentage of the brain tissue may carry out that little amount of metabolism. Specifically, hydrogen peroxide may be used as a co-substrate for the metabolism of ethanol to acetaldehyde by catalase and the action of monoamine oxidase in the monoaminergic neurons would supply the hydrogen peroxide. This production of acetaldehyde may result in the formation of novel metabolites that provide the rewarding stimulus for the consumption of ethanol. To test this hypothesis, a reversible inhibitor of the A-isoform of monoamine oxidase, BW A616U, was compared to irreversible inhibitors of one or both MAO-A and B isoenzymes. Doses of 12.5-75 mg/kg p.o. BW A616U reduced the behavioral effects, ptosis and catalepsy, due to monoamine depletion by 2.5 mg/kg reserpine, but these signs of monoamine depletion were evident 24 h after injection. In the cyanamide-induced drinking rat, 50 mg/kg BW A616U reduced consumption of ethanol by 37%. Phenylzine, an irreversible MAO-A and B inhibitor, reduced consumption of ethanol by 67%, but also food consumption; however, the intake of both increased during the post-treatment period. The MAO-B inhibitor, R(-)-deprenyl, was without effect. Both BW A616U, 50 mg/kg and 75 mg/kg, and 2.0 mg/kg i.p. clorgyline reduced the consumption of ethanol in the genetic drinking Myers high-ethanol preferring (mHEP) rat and reduced the proportion of ethanol consumed to total fluids by over 50%. Again, R(-)-deprenyl was without effect. Clorgyline also markedly reduced the intake of food during the 3-day treatment period, only. However, the consumption of ethanol remained depressed during the 4 days after either 75 mg/kg BW A616U or clorgyline. These data demonstrate that inhibition of MAO-A, but not MAO-B, reduces the volitional consumption of ethanol probably by preventing the formation of both biogenic aldehydes and acetaldehyde so that rewarding alkaloidal products cannot be formed.


Subject(s)
Alcohol Drinking/metabolism , Disease Models, Animal , Monoamine Oxidase/physiology , Volition/physiology , Alcohol Drinking/drug therapy , Animals , Male , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/therapeutic use , Rats , Rats, Sprague-Dawley , Volition/drug effects
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