RESUMEN
Dopaminergic systems are thought to play important roles in the motivational effects of ethanol. In the present experiments, we examined the effects of U99194A, a putative dopamine D(3) receptor antagonist, on ethanol-induced conditioned place preference, locomotor stimulation, taste aversion, and self-administration. In two separate studies with the use of a place conditioning procedure, adult male Swiss-Webster mice received six pairings of a tactile stimulus with ethanol (1 or 3 g/kg, i.p.), U99194A (20 mg/kg, i.p.), or ethanol + U99194A. For determination of ethanol-stimulated activity, subjects received U99194A at a dose of 0, 10, 20, or 30 mg/kg 15 min before ethanol at 0, 1, or 2 g/kg immediately before a 30-min locomotor activity test. In a taste conditioning procedure, subjects received five 1-h access periods to 0.2 M NaCl. After the first four access periods, subjects received ethanol at 0, 2, or 4 g/kg and U99194A at 0, 10, or 20 mg/kg. In an oral self-administration procedure, male C57BL/6J mice received U99194A at 0, 10, or 20 mg/kg, followed by 30-min access to 10% (wt./vol.) sucrose or 10% (vol./vol.) ethanol in 10% sucrose. The acquisition of ethanol-induced conditioned place preference was enhanced by U99194A. However, U99194A did not produce significant preference alone. U99194A did not alter locomotor stimulation produced by an injection of ethanol at 2 g/kg. U99194A also did not alter the acquisition of ethanol-induced conditioned taste aversion and did not change oral ethanol self-administration. These results support the suggestion that dopamine D(3) receptors have specific involvement in ethanol reward, as measured by place conditioning, but are not important for ethanol-stimulated activity, ethanol taste aversion, or ethanol intake.
Asunto(s)
Antagonistas de Dopamina/farmacología , Antagonistas de los Receptores de Dopamina D2 , Etanol/farmacología , Motivación , Animales , Condicionamiento Psicológico/efectos de los fármacos , Condicionamiento Psicológico/fisiología , Relación Dosis-Respuesta a Droga , Indanos/farmacología , Masculino , Ratones , Actividad Motora , Receptores de Dopamina D3RESUMEN
Although several serotonin (5-HT) receptor subtypes influence ethanol consumption, the motivational mechanisms underlying these changes remain unclear. The present experiments characterized the rewarding, aversive and stimulant effects of ethanol in combination with a specific 5-HT1A receptor antagonist (pindobind-5HT1A). In a place conditioning study, adult male Swiss-Webster mice received 6 parings of a distinctive tactile stimulus with either 2 g/kg ethanol, 2.5 mg/kg pindobind-5HT1A, or both drugs in combination. Ethanol-conditioned preference for the tactile cue was enhanced in mice also receiving pindobind-5HT1A, which did not produce cue preference in the absence of ethanol. In a taste conditioning study, Swiss-Webster mice received 4 trials consisting of access to a distinctive NaCl flavor followed by either 4 g/kg ethanol, 2.5 mg/kg pindobind-5HT1A, or both drugs. As expected, ethanol produced avoidance of the flavor. Pindobind-5HT1A did not reduce or enhance ethanol-conditioned flavor aversion. In a study characterizing locomotor activity, 2 g/kg ethanol produced stimulation, which was enhanced after 10 daily treatments. Locomotor sensitization was not altered by co-treatment with pindobind-5HT1A. Overall, the present results show specific effects of 5-HT1A blockade on ethanol reward.
Asunto(s)
Etanol/farmacología , Pindolol/análogos & derivados , Receptores de Serotonina/fisiología , Antagonistas de la Serotonina/farmacología , Animales , Condicionamiento Psicológico/efectos de los fármacos , Señales (Psicología) , Monoterpenos Ciclohexánicos , Habituación Psicofisiológica/efectos de los fármacos , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Pindolol/farmacología , Receptores de Serotonina/efectos de los fármacos , Receptores de Serotonina 5-HT1 , Gusto/efectos de los fármacos , Gusto/fisiología , TactoRESUMEN
RATIONALE: Conditioned taste aversion (CTA) produced by drugs of abuse such as morphine and cocaine has been interpreted as representing the rewarding actions of these drugs. Evidence for this interpretation is based, in part, on findings in rats indicating saccharin is a more effective conditioning flavor compared to salt (NaCl). However, our studies with ethanol have found salt to be a highly effective conditioning flavor in mice. OBJECTIVES: The present series of studies examined the acquisition of CTA to morphine, ethanol, lithium chloride, and cocaine. Further, saccharin and salt were utilized in each experiment in order to determine effectiveness of each flavor to serve as a conditioning stimulus. METHODS: In four separate experiments, adult male DBA/2J mice were acclimated to a 2 h/day water restriction regimen. Subsequently they received four conditioning trials consisting of 1 h access to either 0.15% w/v saccharin or 0.1 M salt followed by 0, 10 or 20 mg/kg morphine (experiment 1), 0, 2, or 4 g/kg ethanol (experiment 2), 0, 1.5 or 3.0 milliequivalents/kg lithium chloride (experiment 3) or 0, 10 or 20 mg/kg cocaine (experiment 4). A fifth flavor access period (trial 5) was not followed by drug exposure. Following trial 5, each subject received 24-h access to the conditioning flavor and water (two-bottle test 1). Control subjects (0 dose groups from each experiment) received a second two-bottle test with 24-h access to both saccharin and salt flavors. RESULTS: Reduced flavor intake and reduced flavor preference was noted in all drug-paired groups in each experiment. However, more rapid development of CTA was seen with the saccharin flavor in morphine- or cocaine-paired groups. In contrast, ethanol-induced CTA appeared more rapidly with the salt flavor. Lithium-induced CTA was modest, and emerged equally with either flavor. CONCLUSIONS: CTA induced by morphine or cocaine in mice occurs in a similar pattern to that seen in rats, and these findings agree with an interpretation based on drug reward. In contrast, ethanol-induced CTA is more likely attributable to aversive effects.