Acute taurine reduced alcohol intake and preference in alcohol-experienced, but not in alcohol-näive rats by central mechanisms.

Taurine is a non-essential ß sulfonated amino acid involved in a plethora of biological functions in the mammalian central nervous system. Taurine is easily accessible in energy drinks for human consumption. Previous preclinical and clinical reports suggest that acute systemic administration of taurine could inhibit some of the behavioral and metabolic effects of alcohol use disorder. Overall, both in rodent and human studies, acute taurine administration reduced voluntary alcohol intake. This study aimed to assess the pharmacological effects of taurine (intracerebroventricular; i.c.v.) on ethanol intake/preference of rats either control (i.e., alcohol naïve) or forced ethanol intake (since juvenile age with a chronic intermittent access model). In addition, to explore anxiety-like behavior (through defensive burying behavior test) as pharmacological control of taurine. We found that acute (i.c.v.) taurine reduced alcohol consumption, i.e., taurine significantly decreased both alcohol intake and preference in adult male Wistar rats. Moreover, taurine elicits an anxiolytic-like effect in all administered groups independently of previous alcohol exposure.

Stress, a Brief Update.

Stress is fundamental for health and adaptation; it is an evolutionarily conserved response that involves several systems in the organism. The study of the stress response could be traced back to the end of the nineteenth century with George Beard's or Claude Bernard's work and, from that moment on, several studies that have allowed the elucidation of its neurobiology and the consequences of suffering from it were consolidated. In this theoretical review, we discuss the most relevant researches to our knowledge on the study of stress response, from the concept of stress, its neurobiology, the hormonal response during stress, as well as its regulation, the effects of acute and chronic stress, stress from cognition, the different stress responses during life, as well as its relationship with different psychiatric disorders. Taken together, the reviewed research updates the classic perspective on stress, increasing the factors that should be considered in research to explore the effects of stress on health.

El estrés es fundamental para la salud y la adaptación; es una respuesta conservada evolutivamente que implica a varios sistemas del organismo. El estudio de la respuesta de estrés se remonta a finales del siglo xix con los trabajos de George Beard o Claude Bernard y a partir de ese momento se consolidaron diversos estudios que han permitido dilucidar su neurobiología y las consecuencias de padecerlo. En esta revisión teórica, abordamos lo más relevante para nuestro conocimiento sobre el estudio de la respuesta de estrés, desde el concepto de estrés, su neurobiología, la respuesta hormonal durante el estrés, así como su regulación, los efectos del estrés agudo y crónico, el estrés desde la cognición, las diferentes respuestas de estrés a lo largo de la vida, además de su relación con diferentes trastornos psiquiátricos. En conjunto, las investigaciones revisadas actualizan la perspectiva clásica sobre el estrés, incrementando los factores que deben tenerse en cuenta en la investigación para explorar los efectos del estrés sobre la salud.

Pharmacologic hyperreactivity of kappa opioid receptors in periaqueductal gray matter during alcohol withdrawal syndrome in rats.

BACKGROUND: Periaqueductal gray matter (PAG) is a brain region rich in kappa-opioid receptors (KOR). KOR in PAG mediates behavioral responses related to pain integration, and panic response, among others. Its participation in the addiction phenomena has been poorly studied. Hence, this preliminary study explored the pharmacological effects of KOR stimulation/blockade in dorsal-PAG (D-PAG) during alcohol withdrawal on anxiety-type behaviors and alcohol intake/preference. METHODS: Juvenile male Wistar rats were unexposed (A-naïve group) or exposed to alcohol for 5 weeks and then restricted (A-withdrawal group). Posteriorly, animals received intra D-PAG injections of vehicle (10% DMSO), salvinorin A (SAL-A; a selective KOR agonist), or 2-Methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine (PF-04455242; a highly selective KOR-antagonist). Subsequently, the defensive burying behavior (DBB) and alcohol intake/preference paradigms were evaluated. RESULTS: SAL-A markedly increased burying time, the height of bedding, and alcohol consumption/preference in A-withdrawal, while slightly increased the height of bedding in A-näive rats. PF-04455242 decreased both burying and immobility duration, whereas increases latency to burying, frequency of rearing, and the number of stretches attempts with no action on alcohol intake/preference in A-withdrawal rats. CONCLUSIONS: In general, stimulation/blockade of KOR in A-withdrawal animals exert higher responses compared to A-naïve ones. SAL-A produced anxiety-like behaviors and increased alcohol consumption/preference, especially/solely in the alcohol-withdrawal condition, while PF-04455242 augmented exploration with no effects on alcohol intake/preference. Our findings suggest a possible pharmacologic hyperreactivity of the KOR in PAG during alcohol withdrawal.

Exposure to anandamide on young rats causes deficits in learning, temporal perception and induces changes in NMDA receptor expression.

Human use of marijuana at an early age has been reported to lead to cognitive impairment. However, researchers have not yet clearly determined whether this impairment is due to marijuana-induced alterations in the developing nervous system and whether this deficit persists into adulthood after marijuana use has ceased. We administered anandamide to developing rats to assess the effect of cannabinoids on development. We subsequently evaluated learning and performance on a temporal bisection task in adulthood and assessed the expression of genes encoding principal subunits of NMDA receptors (Grin1, Grin2A, and Grin2B) in the hippocampus and prefrontal cortex. Rats in two age groups, namely, 21-day-old and 150-day-old rats, received intraperitoneal injections of anandamide or the vehicle for 14 days. Both groups performed a temporal bisection test, which included listening to tones of different durations and classifying them as short or long. The expression of the Grin1, Grin2A and Grin2B mRNAs was evaluated using quantitative PCR in both age groups after extracting mRNA from the hippocampus and prefrontal cortex. We observed a learning impairment in the temporal bisection task (p < 0.05) and changes in the response latency (p < 0.05) in rats that received anandamide. Furthermore, these rats exhibited decreased expression of Grin2b (p = 0.001) compared to those that received the vehicle. In human subjects, the use of cannabinoids during development induces a long-term deficit, but this deficit is not observed in subjects who use cannabinoids in adulthood. Rats treated with anandamide earlier in development took longer to learn the task, suggesting that anandamide exerts a harmful effect on cognition in developing rats. Administration of anandamide during early stages of development induced deficits in learning and other cognitive processes that depend on an adequate estimation of time. The cognitive demands of the environment must be considered when evaluating the cognitive effects of cannabinoids on developing or mature brains. High cognitive demands might induce differential expression of NMDA receptors that improves cognitive capacity, overcoming altered glutamatergic function.

Novel object recognition in Octopus maya.

The Novel Object Recognition task (NOR) is widely used to study vertebrates' memory. It has been proposed as an adequate model for studying memory in different taxonomic groups, allowing similar and comparable results. Although in cephalopods, several research reports could indicate that they recognize objects in their environment, it has not been tested as an experimental paradigm that allows studying different memory phases. This study shows that two-month-old and older Octopus maya subjects can differentiate between a new object and a known one, but one-month-old subjects cannot. Furthermore, we observed that octopuses use vision and tactile exploration of new objects to achieve object recognition, while familiar objects only need to be explored visually. To our knowledge, this is the first time showing an invertebrate performing the NOR task similarly to how it is performed in vertebrates. These results establish a guide to studying object recognition memory in octopuses and the ontological development of that memory.

Defensive and Emotional Behavior Modulation by Serotonin in the Periaqueductal Gray.

Serotonin 5-hydroxytryptamine (5-HT) is a key neurotransmitter for the modulation and/or regulation of numerous physiological processes and psychiatric disorders (e.g., behaviors related to anxiety, pain, aggressiveness, etc.). The periaqueductal gray matter (PAG) is considered an integrating center for active and passive defensive behaviors, and electrical stimulation of this area has been shown to evoke behavioral responses of panic, fight-flight, freezing, among others. The serotonergic activity in PAG is influenced by the activation of other brain areas such as the medial hypothalamus, paraventricular nucleus of the hypothalamus, amygdala, dorsal raphe nucleus, and ventrolateral orbital cortex. In addition, activation of other receptors within PAG (i.e., CB1, Oxytocin, µ-opioid receptor (MOR), and γ-aminobutyric acid (GABAA)) promotes serotonin release. Therefore, this review aims to document evidence suggesting that the PAG-evoked behavioral responses of anxiety, panic, fear, analgesia, and aggression are influenced by the activation of 5-HT1A and 5-HT2A/C receptors and their participation in the treatment of various mental disorders.

Effects on Behavior by Different Exposure Durations of Predator Scent Stress / Efectos Conductuales por Exposición a Diferentes Duraciones de Estrés por Olor de Depredador

Abstract Stress is conceptualized as a systemic response triggered by a stimulus potentially harmful to an organism. Instead of an adaptive outcome, life-threatening experiences may contribute to the development of anxiety disorders and depression. Predator scent stress (PSS) is one of the most utilized rodent models of stress-induced psychopathology, in which rodents are exposed to a volatile predator cue that signifies imminent danger. It is unclear if the duration of a life-threatening experience could have differential consequences on the expression of anxiety-like and depression-like behaviors. For this reason, the goal of this present study was to evaluate the effect of different exposure durations (3 min., 10 min., or 20 min.) to the scent of bobcat urine. Wistar rats housed under 12/12 dark cycle in standard laboratory conditions were exposed to the PSS model and 24 hrs. after the stressor, behavioral consequences were evaluated in the open field test, saccharin preference test, and forced swim test. The results obtained show that a 10-minute exposure is sufficient to induce an anxiety-like and a depression-like behavioral profile. We conclude that the time exposure could be a major variable to obtain clear and trustable results and to avoid overexposure to stressor.

Resumen El estrés es una respuesta sistémica desencadenada por un estímulo potencialmente peligroso para el organismo. Esta respuesta permite al organismo adaptarse a la condición estresante, sin embargo, experiencias que amenazan a la vida pueden incrementar el riesgo de desarrollar trastornos de ansiedad y depresión. La exposición al olor de depredador (EOD) es el modelo animal de patología inducida por estrés más utilizado. Consta de la exposición a una pista olfativa que significa peligro inminente. Aún no está claro si la duración a una experiencia que amenaza la vida puede generar diferencias en la expresión conductas tipo-ansiedad o tipo-depresión. Por esta razón, el objetivo de este estudio fue evaluar el efecto de diferentes duraciones de exposición (3 min., 10 min. o 20 min.) al aroma de lince. Se utilizaron ratas hembra de la cepa Wistar en un ciclo luz oscuridad 12/12 en condiciones estándar de laboratorio, los sujetos fueron evaluados en la prueba de campo abierto, preferencia de sacarina y nado forzado 24 hrs. después de terminado el estresor. Los resultados indican que la exposición a 10 min. es suficiente para inducir el perfil conductual tipo-depresión y tipo-ansiedad. Concluimos que el tiempo de exposición puede ser una variable de mayor importancia para obtener resultados confiables y prevenir exposiciones innecesarias al estrés.

Diferencias intra-especie en respuesta al estrés: Hacia enfoques traslacionales / Intra-specie differences in response to stress: Looking for translational view

Resumen: El estrés produce la sobreactivación del eje HPA y sistema neuroendocrino. Se ha mostrado que existe daño en estructuras relacionadas con el procesamiento emocional (amígdala) aprendizaje (hipocampo), toma de decisiones y prospección (corteza prefrontal). Sin embargo, se generalizan los efectos del estrés sin ponderar el tipo de estrés (crónico o agudo), duración, especie, etc. Esto permite que hallazgos se contrapongan a nivel cortical, neuroquímico, hormonal y conductual. El objetivo fue evaluar los efectos del estrés crónico impredecible (ECI) en diferentes cepas de ratas y sus efectos inmediatos o a largo plazo. Se utilizaron ratas macho Wistar, Wistar Kyoto y SHR en condiciones estándar de laboratorio. Se aplicó una batería de ECI y una batería de evaluación conductual para evaluar efectos previos, agudos y crónicos. La cepa Wistar Kyoto muestra deficiencias previas a la exposición. La cepa SHR muestra mayor movilidad y sesgos atencionales, lo que produce un efecto que perdura a largo plazo. La cepa Wistar muestra una gran capacidad de adaptación ya que aunque se observaron deficiencias inmediatamente después de la exposición al estrés, éstas se recuperan e largo plazo. Se infiere que las precondiciones de los sujetos podrían funcionar como biomarcadores y poder prevenir padecimientos relacionados al estrés.

Abstract: Stress produces the over activation of the Hypothalamus Pituitary Adrenal axis (HPA) and the neuroendocrine system. It has been shown that it could damage structures related with the emotional processing (amygdala), learning and memory (Hippocampus), decision making and prospection (prefrontal cortex). However, the stress affects are generalized without weighting all the elements related with this conditions, for example the kind of stress stimuli (acute or chronic), duration, species, etc. This allowed that some findings it will go against each other in relation to cerebral cortex function, neurochemical, hormonal and behavioral. The main porpoise of this research was to evaluate the effects of the unpredictable chronic stress on several rat strains (Wistar, Wistar Kyoto and SHR) and its immediate effects or in long term so. Wistar, Wistar Kyoto and SHR rats were used. All animals were housed in standard laboratory conditions and we follow the international guide for use and care of laboratory animals. The subjects were exposed to the Chronic Unpredictable Stress Battery (CUSB) and to evaluate the stress effects all the subjects were evaluated with a Battery of Behavioral Evaluation to find the previous, immediate or the long-term effects of CUSB exposition. The Wistar Kyoto strain showed deficits before the stress exposure. Whereas the SHR rats showed more mobility and poor attention which produces a long-term effect. The Wistar strain show a high adaptation to the adverse conditions because until the animals showed strong effects immediately after the stress exposure they showed a good recovery in the long term. In conclusion we can asseverate that the preconditions in every strain plays a major role in the stress response and that preconditions it could be used as biomarkers and in that way infer if the subjects are more susceptible to suffer high stress or some other related disease.

Efecto de la Nicotina en un Modelo de Activación Dopaminérgica en Timing: Hacia un Modelo en Esquizofrenia / Nicotine Effect on a Model of Hyperactivation of the Dopaminergic System using a Temporal Bisection Task: Towards a Model in Schizophrenia

Resumen: La esquizofrenia es un trastorno que implica múltiples anomalías bioquímicas. Los pacientes con esquizofrenia tienen una prevalencia muy alta de tabaquismo, que se ha relacionado con el hecho de que la nicotina tiene importantes interacciones con la dopamina, siendo teóricamente capaz de reducir algunos de los síntomas positivos, negativos y cognitivos de la esquizofrenia. Sin embargo, existe controversia respecto al papel de la nicotina en la sintomatologia de los pacientes con esquizofrenia fumadores. El objetivo de la presente investigación fue evaluar el efecto de la administración de nicotina en un modelo de hiperactivación del sistema dopaminérgico, mediante una tarea de estimación temporal en animales del laboratorio. Los resultados sugieren una recuperación de las habilidades cognitivas, sin embargo el efecto procognitivo de la nicotina depende de una gran variedad de factores, incluyendo los sistemas neurales subyacentes a las tareas usadas y su interacción con otros fármacos y sistemas. Se propone que la evaluación del procesamiento de la información temporal puede servir como una herramienta en la comprensión y evaluación de los déficits cognitivos de la esquizofrenia.

Abstract: Schizophrenia is a disorder that involves multiple biochemical abnormalities. Patients with schizophrenia have a high prevalence of smoking, which has been linked with the fact that nicotine has significant interactions with dopamine, theoretically being able to reduce some of the positive, negative and cognitive symptoms of schizophrenia. However, there is controversy about the role of nicotine on symptoms of patients with schizophrenia who smoke. The objective of this research was to evaluate the effect of nicotine administration in a model of hyperactivation of the dopaminergic system using a temporal bisection task. The results suggest a recovery of cognitive skills, but the procognitive effect of nicotine depends on a variety of factors, including the underlying neural systems of the tasks and its interaction with other drugs and systems. It is proposed that the evaluation of the temporal processing of information could be a tool in the understanding and assessment of cognitive deficits of schizophrenia.

The effect of carmustine on Bergmann cells of the cerebellum.

Administration of the alkylating agent carmustine to pregnant mice induces hyperlocomotion in the offspring. Motor performance was evaluated by the rotarod task, which revealed that these animals have diminished Grab Frequency and a higher Performance Index, whereas Error of Latency and Latency to Fall were unaffected. Considering the recently revealed role of Bergmann cells of cerebellum in the control of motor activity, we used the transgenic mice GFAP-GFP to explore the impact of carmustine on the organization of these glial cells. Multiple examples of cell layer disorganization were detected; many soma of Bergmann cells were displaced to the external cell layer, and their processes were not well defined until young adulthood. In addition, the roof of the fourth ventricle was convoluted. These observations suggest that the exacerbated locomotion induced by carmustine may be due, in part, to the altered organization of the cell layers of cerebellum.

Subjective and Real Time: Coding Under Different Drug States.

Organisms are constantly extracting information from the temporal structure of the environment, which allows them to select appropriate actions and predict impending changes. Several lines of research have suggested that interval timing is modulated by the dopaminergic system. It has been proposed that higher levels of dopamine cause an internal clock to speed up, whereas less dopamine causes a deceleration of the clock. In most experiments the subjects are first trained to perform a timing task while drug free. Consequently, most of what is known about the influence of dopaminergic modulation of timing is on well-established timing performance. In the current study the impact of altered DA on the acquisition of temporal control was the focal question. Thirty male Sprague-Dawley rats were distributed randomly into three different groups (haloperidol, d-amphetamine or vehicle). Each animal received an injection 15 min prior to the start of every session from the beginning of interval training. The subjects were trained in a Fixed Interval (FI) 16s schedule followed by training on a peak procedure in which 64s non-reinforced peak trials were intermixed with FI trials. In a final test session all subjects were given vehicle injections and 10 consecutive non-reinforced peak trials to see if training under drug conditions altered the encoding of time. The current study suggests that administration of drugs that modulate dopamine do not alter the encoding temporal durations but do acutely affect the initiation of responding.

El Amaranto como Fuente de Reforzamiento: Un Estudio con Roedores / Amaranth as Reinforcement Source: A Rodent Study

Resumen: El presente estudio evalúa el amaranto como una alternativa a los reforzadores que se utilizan en la actualidad en los laboratorios experimentales con roedores. Se compararon diversos elementos como la preferencia de consumo, la motivación y el valor reforzante entre tres tipos de alimentos (dos tipos de pellets y amaranto) mediante cuatro experimentos con laberinto radial y consumo libre en 11 ratas de la cepa Wistar. Los resultados muestran que el amaranto tiene un alto valor reforzante ya que, se observó preferencia por su consumo comparado con los demás alimentos. Se propone al amaranto como una buena alternativa para usarse como reforzador con varias ventajas como la preferencia de consumo, su valor reforzante, su fácil accesibilidad en el país y que es más económico que los pellets importados.

Abstract: This study evaluates amaranth as an alternative to reinforcers which are currently used in experimental laboratories with rodents. We compared some elements such as consumer preference, motivation and reinforcing value of three types of food (two types of pellets and amaranth) through four experiments with free radial maze and free consumption in 11 Wistar rats. The results show that amaranth has a high reinforcing value. Also, there was a preference for amaranth consumption compared with the other two reinforcers. Amaranth is proposed as a good alternative for use as a reinforcer with several advantages such as consumer preference, its reinforcing value, accessibility in the country and that it is cheaper than the usual pellets.

Evaluación de la Nicotina como Estímulo Aversivo / Nicotine Assessment as an Aversive Stimulus

La nicotina es el ingrediente psicoactivo del tabaco y se ha descrito como aversiva, reforzante o procognitiva. Sin embargo no existe mucha investigación sobre el sobrelapamiento de los efectos dosis-dependientes como estímulo aversivo y procognitiva. Por lo que evaluaremos los efectos de la nicotina en el paradigma de condicionamiento aversivo al sabor (CAS), con el objetivo de obtener una curva dosis-respuesta del efecto aversivo y compararlo con los efectos procognitivos reportados. Se utilizaron 20 ratas macho Wistar asignadas aleatoriamente a cinco grupos (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). Los resultados muestran tendencia al decremento dosis-dependiente con efecto máximo en la dosis de 1.6 mg/kg, sin embargo se hallaron efectos a partir de la dosis de 0.8 mg/kg lo cual sobrelapa con las dosis propuestas con efectos procognitivos. Esto nos permite proponer que algunos efectos puedan deberse a efectos aversivos periféricos más que a centrales.

Nicotine is the main ingredient of tobacco and it has been described as aversive, reinforce and procognitive. However there is not enough research about the overlapping of the dose-dependent effects as aversive stimulus and precognitive effects. For those reasons we evaluated the nicotine effects on the Conditioned Taste Aversion paradigm (CTA) to evaluated the dose-response curve of the aversive effects of nicotine and to compare such effects with the procognitive effects reported. 20 male Wistar rats in standard laboratory conditions were randomly assigned to 5 groups (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). The obtained results showed a dose-dependent decrease with a maximum effect at 1.6 mg/kg dose, however we founded effects from the 0.8 mg/kg dose, such dose overlapped with procognitive doses reported. These results allow us to propose that some effects could be due the periferical aversive effects instead of the central procognitive effects.

Dorsolateral frontal cortex and peripheral muscarinic receptors participation in the discriminative stimulus properties of scopolamine in rats.

Organisms are capable of making decisions based on their ability to discriminate between different stimuli. This principle is fundamental for the adaptation of organisms to their environment, by emitting appropriate behaviors based on a previously acquired discriminative process. The present study analyzed the participation of the peripheral nervous system, the M1 muscarinic receptor subtype, as well as the contribution of the dorsolateral frontal cortex to discrimination process using scopolamine as discriminative stimulus. Male Wistar rats were trained to discriminate between scopolamine (1.0 mg/kg) and saline injections (i.p.) using a two-lever operant procedure. Once discrimination was acquired, generalization curves for scopolamine, methylscopolamine, pirenzepine, dorsolateral frontal cortex lesion and control conditions were obtained. Results showed that rats were able to discriminate and generalize its responses to different doses of scopolamine but not for methylscopolamine or pirenzepine, thus the data suggest that discriminative properties of scopolamine are processed in CNS and that the M1 receptor does not participate in this process. Dorsolateral frontal cortex lesion did not produce any statistically significant difference in the generalization curve, which suggests that a system different from the dorsolateral prefrontal cortex may be responsible for the control of stimulus produced by scopolamine.

Evaluación de la nicotina como estímulo aversivo / Nicotine Assessment as an Aversive Stimulus

La nicotina es el ingrediente psicoactivo del tabaco y se ha descrito como aversiva, reforzante o procognitiva. Sin embargo no existe mucha investigación sobre el sobrelapamiento de los efectos dosis-dependientes como estímulo aversivo y procognitiva. Por lo que evaluaremos los efectos de la nicotina en el paradigma de condicionamiento aversivo al sabor (CAS), con el objetivo de obtener una curva dosis-respuesta del efecto aversivo y compararlo con los efectos procognitivos reportados. Se utilizaron 20 ratas macho Wistar asignadas aleatoriamente a cinco grupos (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). Los resultados muestran tendencia al decremento dosis-dependiente con efecto máximo en la dosis de 1.6 mg/kg, sin embargo se hallaron efectos a partir de la dosis de 0.8 mg/kg lo cual sobrelapa con las dosis propuestas con efectos procognitivos. Esto nos permite proponer que algunos efectos puedan deberse a efectos aversivos periféricos más que a centrales.

Nicotine is the main ingredient of tobacco and it has been described as aversive, reinforce and procognitive. However there is not enough research about the overlapping of the dose-dependent effects as aversive stimulus and precognitive effects. For those reasons we evaluated the nicotine effects on the Conditioned Taste Aversion paradigm (CTA) to measure the dose-response curve of the aversive effects of nicotine and to compare such effects with the procognitive effects reported. 20 male Wistar rats in standard laboratory conditions were randomly assigned to 5 groups (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). The obtained results showed a dose-dependent decrease with a maximum effect at 1.6 mg/kg dose; however we founded effects from the 0.8 mg/kg dose, such dose overlapped with procognitive doses reported. These results allow us to propose that some effects could be due the periferical aversive effects instead of the central procognitive effects.

Timing and anticipation: conceptual and methodological approaches.

Anticipation occurs on timescales ranging from milliseconds to hours to days. This paper relates the theoretical and methodological developments in the study of interval timing in the seconds, minutes and hours range to research on the anticipatory activity induced by regularly timed daily meals. Daily food-anticipatory activity (FAA) is entrained by procedures which are formally identical to procedures studied in Pavlovian and operant conditioning except for the long duration of the interval between feeding opportunities. As in FAA, the conditioning procedures induce orderly anticipatory activity in advance of food presentation. During the interval between foods the behaviors that express anticipation change as the interval progresses. Consequently, no single response represents a pure measure of anticipation. The ability to distinguish between properties of general anticipatory timing mechanisms such as the scalar property (Gibbon, 1977) and dynamic properties of specific response output systems has been facilitated by teaching animals to use arbitrary anticipatory responses like bar-pressing to obtain food. Interval timing research highlights the importance of identifying the mechanisms of perception, memory, decision making and motivation that all contribute to food anticipation. We suggest that future work focused on the similarities and differences in the neural bases of FAA and interval timing may be useful in unravelling the mechanisms mediating timing behavior.

The GABA-B antagonist 2-hydroxysaclofen reverses the effects of baclofen on the discriminative stimulus effects of D-amphetamine in the conditioned taste aversion procedure.

Some of the behavioral effects of d-amphetamine (d-AMPH) are mediated by an increase in dopamine neurotransmission in the nucleus accumbens. However, there is evidence that gamma-amino-butyric-acid-B (GABA-B) receptors are involved in some behavioral effects of D-AMPH and cocaine. Here, we examined the effects of baclofen on the discriminative stimulus properties of D-AMPH, using conditioned taste aversion (CTA) as the drug discrimination procedure. Male Wistar rats were deprived of water and trained in the CTA procedure. They received D-AMPH (1 mg/kg, i.p.) before gaining access to saccharin, which was followed by an injection of LiCl. On alternate days, the subjects received saline before and after the access to saccharin. After the rats learned the D-AMPH-saline discrimination, the standard dose of D-AMPH was replaced by different doses of D-AMPH, baclofen (a GABA-B receptor agonist), 2-hydroxysaclofen (a GABA-B receptor antagonist), a combination of baclofen+D-AMPH, or a combination of 2-hydroxysaclofen+baclofen+D-AMPH. Baclofen did not substitute for D-AMPH, but, when combined with D-AMPH, it produced a small but significant decrease in the discriminative stimulus effects of D-AMPH. This effect was reversed by administration of 2-hydroxysaclofen. These data suggest that GABA-B receptors play a regulatory role in the discriminative stimulus effects of D-AMPH.