Ethanol induces a dose-dependent conditioned place preference and conditioned place aversion in Japanese quail.

The conditioned place preference (CPP) paradigm is commonly used to investigate the motivational properties of drugs of abuse. Cues in the environment may become paired with these motivational properties and later result in drug seeking. Because many of these alcohol-paired cues are visual, Japanese quail may be a beneficial model to examine visual cue-induced alcohol seeking behavior. The aim of the present study was to examine the motivational properties of ethanol using a visual CPP model. During CPP, quail were given an initial preference test to determine their initially preferred chamber, during which time they could explore the entire chamber for 15 min. Following the initial preference test, quail were gavaged with their assigned treatment (water or 0.75 or 2.0 g/kg of ethanol) and were confined to their initially least preferred chamber every other conditioning day for 30 min. On alternate days, they were gavaged with water and confined to the preferred chamber for 30 min. After the 8th day of conditioning, a final preference test was given. Locomotor activity was also measured during conditioning. The findings indicated that quail that received the 0.75 g/kg ethanol developed a place preference to the ethanol-paired chamber, and that quail treated with 2 g/kg ethanol developed a place aversion to the ethanol-paired chamber. Additionally, locomotor activity was reduced in quail that received the high dose of ethanol. The findings suggest that both the rewarding and aversive properties of ethanol may be observable in this visual cue CPP model. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sex differences in alcohol dehydrogenase levels (ADH) and blood ethanol concentration (BEC) in Japanese quail.

Ethanol is one of the most widely used and abused drugs. Following ethanol consumption, ethanol enters the bloodstream from the small intestine where it gets distributed to peripheral tissues. In the bloodstream, ethanol is cleared from the system by the liver. The primary metabolism of ethanol uses alcohol dehydrogenase (ADH). In mammals, females appear to have higher ADH activity in liver samples than males. The purpose of the first experiment was to analyze sex differences in ADH levels following 12 d of ethanol administration (i.e., water or 2 g/kg) in male and female quail. Following the last daily treatment of ethanol, quail were euthanized, their livers were extracted, and ADH was analyzed in liver homogenate samples. Results showed that female quail had higher ADH levels, heavier livers, and a greater liver to body weight ratio than male quail. In a second experiment, we aimed to develop a blood ethanol concentration (BEC) profile for both male and female quail. Quail were administered 0.75 or 2 g/kg of ethanol and blood was collected at 0.5, 1, 2, 4, 6, 8, 12, 24 h after gavage administration. Blood ethanol concentration was analyzed using an Analox. We found that quail had a fairly rapid increase in BECs followed by a steady and slow disappearance of ethanol from the blood samples. Female quail had a lower peak of ethanol concentration and a smaller area under the curve (AUC) than male quail. The current research suggests that higher ADH levels in female quail may be responsible for increased metabolism of ethanol. In general, quail appear to eliminate ethanol more slowly than rodents. Thus, as a model, they may allow for a prolonged window with which to investigate the effects of ethanol.

Age-dependent effects of dopamine receptor inactivation on cocaine-induced behaviors in male rats: Evidence of dorsal striatal D2 receptor supersensitivity.

N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), which irreversibly inactivates dopamine (DA) receptors, causes pronounced age-dependent behavioral effects in rats. For example, EEDQ either augments or does not affect the DA agonist-induced locomotor activity of preweanling rats while attenuating the locomotion of adolescent and adult rats. The twofold purpose of this study was to determine whether EEDQ would: (a) potentiate or attenuate the cocaine-induced locomotor activity of preweanling, adolescent, and adult rats; and (b) alter the sensitivity of surviving D2 receptors. Rats were treated with vehicle or EEDQ (2.5 or 7.5 mg/kg) on postnatal day (PD) 17, PD 39, and PD 84. In the behavioral experiments, saline- or cocaine-induced locomotion was assessed 24 hr later. In the biochemical experiments, dorsal striatal samples were taken 24 hr after vehicle or EEDQ treatment and later assayed for NPA-stimulated GTPγS receptor binding, G protein-coupled receptor kinase 6 (GRK6), and ß-arrestin-2 (ARRB2). GTPγS binding is a direct measure of ligand-induced G protein activation, while GRK6 and ARRB2 modulate the internalization and desensitization of D2 receptors. Results showed that EEDQ potentiated the locomotor activity of preweanling rats, while attenuating the locomotion of older rats. NPA-stimulated GTPγS binding was elevated in EEDQ-treated preweanling rats, relative to adults, indicating enhanced functional coupling between the G protein and receptor. EEDQ also reduced ARRB2 levels in all age groups, which is indicative of increased D2 receptor sensitivity. In sum, the present results support the hypothesis that D2 receptor supersensitivity is a critical factor mediating the locomotor potentiating effects of EEDQ in cocaine-treated preweanling rats.

A glucocorticoid receptor antagonist reduces sign-tracking behavior in male Japanese quail.

Addiction is characterized as a chronic debilitating disease. One devastating feature of addiction is the susceptibility of relapse (40-60%) after stretches of abstinence. One theory that may account for relapse suggests that drug cues (e.g., paraphernalia) may increase stress hormones, and this may prompt relapse. Repeatedly pairing a neutral cue with a reward is commonly utilized to measure what subjects learn about a cue that is predictive of reward. Research has shown that animals that attend to a cue more than to the reward (sign trackers) may be more vulnerable to drug addiction. Additionally, research has shown that sign tracking is associated with an increase in corticosterone, a primary stress hormone. PT150 is a novel glucocorticoid receptor antagonist that moderates the release of corticosterone. In the current experiment, it was hypothesized that subjects given repeated administration of PT150 would reduce sign tracking compared to subjects given placebo. Time spent (in seconds) near a cue that predicts reward (conditional stimulus) served as a measure of sign tracking, and PT150 or placebo was administered following sign tracking. An independent-samples t test revealed that subjects that received PT150 had reduced time spent near the conditioned stimulus compared to controls. Given the devastating effects of drug addiction, identification of a potential pharmacological intervention in the reduction of relapse would be of great value. Therefore, future research is needed to validate the use of PT150 in reducing behaviors associated with drug addiction. (PsycINFO Database Record

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats.

RATIONALE: The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. OBJECTIVE: The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. METHODS: In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. RESULTS: Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. DISCUSSION: These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.

Age-dependent changes in cocaine sensitivity across early ontogeny in male and female rats: possible role of dorsal striatal D2(High) receptors.

RATIONALE: Responsiveness to acute psychostimulant administration varies across ontogeny. OBJECTIVE: The purpose of the present study was to determine if age-dependent changes in D2(High) receptors may be responsible for the ontogeny of cocaine sensitivity in preweanling, adolescent, and adult rats. METHODS: [(3)H]-Domperidone/dopamine competition assays were used to determine ontogenetic changes in the proportion of D2(High) receptors in male and female preweanling [postnatal day (PD) 5, 10, 15, and 20], adolescent (PD 40), and adult (PD 80) rats. In the behavioral experiment, responsiveness to cocaine (2.5, 5, 10, or 20 mg/kg) was assessed on PD 20, PD 40, and PD 80 for 60 min. Male and female rats were habituated to the apparatus on the 2 days prior to testing. Distance traveled data were presented both untransformed and as percent of saline controls. RESULTS: Male and female preweanling rats (PD 5-PD 20) had a significantly greater percentage of dorsal striatal D2(High) receptors than adolescent or adult rats. Likewise, preweanling rats (PD 20) were more sensitive to the behavioral effects of cocaine than the two older age groups. Adolescent and adult rats responded in a generally similar manner; however, analysis of the untransformed locomotor activity data suggested that adolescent rats were hyporesponsive to 2.5 and 20 mg/kg cocaine when compared to adults. CONCLUSIONS: Data from the present study are consistent with the hypothesis that ontogenetic changes in D2(High) receptors are responsible for age-dependent differences in psychostimulant sensitivity.

Nicotine exposure beginning in adolescence enhances the acquisition of methamphetamine self-administration, but not methamphetamine-primed reinstatement in male rats.

BACKGROUND: Nicotine is commonly abused in adolescence and is believed to be a "gateway" to other drugs of abuse [e.g., methamphetamine (METH)]. The relationship between early nicotine exposure and later METH use is complicated because the majority of juvenile smokers continue to use cigarettes into adulthood. Thus, the present investigation examined the individual and combined contribution of adolescent and adult nicotine exposure on METH self-administration. METHODS: Forty-three male rats were pretreated with saline or nicotine (0.16 or 0.64 mg/kg, SC) from postnatal day (PD) 35-50. On PD 51, subjects were split into the following groups: SAL-SAL, 0.16-0.16, 0.16-SAL, 0.64-0.64, and 0.64-SAL. Rats were then trained to lever press for METH (0.05 mg/kg) for seven days on an FR1 and seven days on an FR3 reinforcement schedule. After acquisition training, rats underwent 14 days of extinction and were then tested for METH-induced primed reinstatement (1.0mg/kg, IP). RESULTS: Data showed that rats receiving continuous injections of the low dose of nicotine (0.16-0.16) obtained more METH infusions versus the control group (SAL-SAL) on an FR1 and FR3 schedule. In addition, rats on the FR3 schedule that received a low dose of nicotine during the adolescent period only (0.16-SAL) had more METH intake than the control group (SAL-SAL). Interestingly, the high dose of nicotine exposure had no effect on METH intake and neither nicotine dose altered METH seeking behavior. CONCLUSIONS: Low dose exposure to nicotine during adolescence enhances the reinforcing effects of METH, while heavier exposure has no effect on METH intake.