RESUMEN
Differences in the mesolimbic dopamine (DA) pathway that regulates alcohol preference may also increase sensitivity to the reinforcing effects of other drugs of abuse. In the present study, the curve-shift (rate-frequency) paradigm was used to quantify the interaction of amphetamine with the rewarding effects of lateral hypothalamic brain stimulation reward (BSR) in alcohol-preferring (P) and -nonpreferring (NP) rats. The role of D-sub-1 and D-sub-2 DA receptors of the nucleus accumbens (NAcc) in mediating the reward-potentiating effects of amphetamine was also determined. Animals were tested with randomly administered amphetamine (0.25, 0.75, 1.25 mg/kg ip), DA-receptor antagonists (SCH 23390 [2.0 microg, 5.0 microg]; eticlopride [2.0 microg, 5.0 microg]), or a combination of the 2 (SCH 23390 [2.0 microg, 5.0 microg] + 0.75 mg/kg amphetamine; eticlopride [2.0 microg, 5.0 microg] + 0.75 mg/kg amphetamine). Amphetamine produced comparable dose-related leftward shifts in the rate-frequency function for both P and NP rats, with a greater than 60% reduction observed in BSR threshold. On intervening days, baseline threshold was unaltered between tests and similar between rat lines. Unilateral infusion in the NAcc of either the D-sub-1 or D-sub-2 receptor antagonist produced rightward shifts in the rate-frequency function of amphetamine, completely reversing-attenuating its reward-enhancing effects. The results demonstrate that amphetamine produces similar threshold-lowering effects in both P and NP rats and that the reward-potentiating effects of amphetamine do not correlate with alcohol preference under the conditions of the present study.
Asunto(s)
Consumo de Bebidas Alcohólicas , Anfetaminas/farmacología , Motivación , Núcleo Accumbens/efectos de los fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Animales , Benzazepinas/farmacología , Antagonistas de Dopamina/farmacología , Estimulación Eléctrica , Electrodos , Masculino , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiología , Ratas , Salicilamidas/farmacologíaRESUMEN
BACKGROUND: The relation between ethanol (EtOH) preference and sensitivity to brain stimulation reward (BSR) was examined under multiples schedules of reinforcement in the current study. For comparison, the study also examined the relation between EtOH preference and motivation for a sweet, palatable sucrose solution under similar schedules of reinforcement. METHODS: To investigate sensitivity to BSR performance, alcohol-preferring and -nonpreferring rats were tested using the curve-shift (rate-frequency) paradigm under several intensity levels during a 20-min session. Animals were first trained under an optimal current intensity, which produced maximal responding (i.e., 100%) across a series of descending frequencies (i.e., 300-20 Hz). BSR was then evaluated at 100%, 75%, and 50% of the optimal current. The sensitivity of the curve-shift method was further evaluated under the animal's optimal current using the FR1, FR6, and FR12 schedules. To examine responding for the sucrose solution, a separate group of alcohol-preferring and -nonpreferring rats was initially stabilized on an FR1 schedule and then subsequently on FR6 and FR12 schedules. RESULTS: The results demonstrated that reducing the reinforcing efficacy of BSR via reduction in current intensity/reinforcement schedule produced marked orderly rightward shifts in the rate-frequency curves relating responding to stimulation frequency in both rat lines. However, no differences were found between the lines with either manipulation. Specifically, both lines demonstrated orderly reductions in response rate and increases in BSR threshold parameters (i.e., half maximal frequency/responding, minimum and maximum frequencies). In contrast to BSR, genetic selection for EtOH preference was highly associated with responding for the sweet, palatable sucrose solution. The association was even more salient as the reinforcement schedule increased (i.e., reward cost). CONCLUSION: The results demonstrate that responding for BSR is not associated with EtOH preference, insofar as alcohol-preferring and -nonpreferring rats respond similarly under an array of reinforcement schedules and current intensities. In contrast, genetic selection for EtOH preference is highly associated with responding for a palatable sucrose reward, and the relation increases as the reward cost for the sucrose increases. These findings suggest that similar/overlapping mechanisms of action regulate the reinforcing properties of EtOH and sucrose but that overlapping yet distinct neuronal mechanism may modulate the reward characteristics of BSR and EtOH preference.