Amphetamine lowers brain stimulation reward (BSR) threshold in alcohol-preferring (P) and non-preferring (NP) rats: Regulation by D₁ and D₂ receptors in the nucleus accumbens

• Published in: Experimental and clinical psychopharmacology 2006-08, Vol.14 (3), p.361-376
• Main Authors: Eiler, William J. A., Masters, Jacob, McKay, Pete F., Hardy, Lathen, Goergen, Josh, Mensah-Zoe, Boikai, Seyoum, Regat, Cook, Jason, Johnson, Nathan, Neal-Beliveau, Bethany, June, Harry L.
• Format: Article
• Language: English
• Subjects: Amphetamines; Animal; Brain Stimulation; Dopamine Antagonists; Drug Interactions; Drug Sensitivity; Ethanol; Male; Medial Forebrain Bundle; Neural Receptors; Nucleus Accumbens; Rats; Rewards; Thresholds
• ISSN: 1064-1297; 1936-2293
• DOI: 10.1037/1064-1297.14.3.361

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 D₁ and D₂ 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 μg, 5.0 μg]; eticlopride [2.0 μg, 5.0 μg]), or a combination of the 2 (SCH 23390 [2.0 μg, 5.0 μg] + 0.75 mg/kg amphetamine; eticlopride [2.0 μg, 5.0 μg] + 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 D₁ or D₂ 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. (PsycInfo Database Record (c) 2023 APA, all rights reserved) (Source: journal abstract)