RESUMEN
The bed nucleus of the stria terminalis (BNST) has been reported to release increased levels of extracellular dopamine (DA) following the systemic administration of abused drugs in outbred rats. This study examined the BNST as a novel locus for supporting operant responding for brain stimulation reward (BSR) in rats bred for alcohol preference while determining any potentiating effects of ethanol (EtOH) (0.125-1.25 g/kg, i.p.) and amphetamine (0.25-1.60 mg/kg, i.p.) on BSR within the BNST. Also examined was the capability of D1 receptor blockade to attenuate any observed potentiation. Following surgical implantation, alcohol-preferring (P) and non-preferring (NP) rats responded to a range of descending frequencies (300-20 Hz) as evaluated by a rate-frequency paradigm. The results revealed that the BNST was capable of supporting BSR in P but not NP rats. Also, amphetamine pretreatment produced a significant leftward shift in the rate-frequency function in P rats with significant reductions observed in three other measures of reward threshold, while EtOH only lowered the minimum frequency needed to produce responding. The effects of systemic amphetamine were successfully attenuated by the unilateral infusion of the D1 receptor antagonist SCH 23390 (5.0 microg) into the contralateral nucleus accumbens. The results suggest the BNST is capable of supporting BSR performance in P, but not NP rats, possibly due to increased sensitivity to the electrical stimulation-induced DA release of BSR in the innately DA "deficient" limbic system of P rats.
Asunto(s)
Consumo de Bebidas Alcohólicas , Alcoholes/farmacología , Anfetamina/farmacología , Condicionamiento Operante/efectos de los fármacos , Inhibidores de Captación de Dopamina/farmacología , Recompensa , Núcleos Septales/fisiología , Consumo de Bebidas Alcohólicas/psicología , Análisis de Varianza , Animales , Conducta Animal/efectos de los fármacos , Benzazepinas/farmacología , Condicionamiento Operante/fisiología , Antagonistas de Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Estimulación Eléctrica/métodos , Preferencias Alimentarias/efectos de los fármacos , Preferencias Alimentarias/fisiología , Masculino , Ratas , Núcleos Septales/efectos de los fármacos , Núcleos Septales/efectos de la radiaciónRESUMEN
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.