title: Amphetamine lowers brain stimulation reward (BSR) threshold in alcohol-preferring (P) and -nonpreferring (NP) rats: regulation by D-sub-1 and D-sub-2 receptors in the nucleus accumbens.
abstract: 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.
authors.affiliation: Department of Psychology, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 21201, USA.
authors.forename: William J A
authors.initials: WJ
authors.lastname: Eiler
authors.forename: Jacob
authors.initials: J
authors.lastname: Masters
authors.forename: Pete F
authors.initials: PF
authors.lastname: McKay
authors.forename: Lathen
authors.initials: L
authors.lastname: Hardy
authors.forename: Josh
authors.initials: J
authors.lastname: Goergen
authors.forename: Boikai
authors.initials: B
authors.lastname: Mensah-Zoe
authors.forename: Regat
authors.initials: R
authors.lastname: Seyoum
authors.forename: Jason
authors.initials: J
authors.lastname: Cook
authors.forename: Nathan
authors.initials: N
authors.lastname: Johnson
authors.forename: Bethany
authors.initials: B
authors.lastname: Neal-Beliveau
authors.forename: Harry L
authors.initials: HL
authors.lastname: June
mesh_terms: D000428:Alcohol Drinking; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D004566:Electrodes; D008297:Male; D009042:Motivation; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C045989:eticlopride