The reward cost potentiates amphetamine reinforcing actions in high alcohol drinking (HAD), but not low alcohol drinking (LAD) rats: Regulation by D1, but not D2 dopamine receptors of the nucleus accumbens

James Espa Woods, Purdue University

Abstract

Selective breeding is a valuable tool for identifying characteristics that are associated with and predict vulnerability to drug abuse. In the replicate 1 high alcohol drinking (HAD) and low alcohol drinking (LAD) rat lines, the curve-shift (rate frequency) paradigm was used to quantify the interaction of amphetamine (AMPH) with the rewarding effects of lateral hypothalamic brain stimulation reward (BSR). HAD-1 and LAD-1 rats were tested at 72 hr intervals with increasing doses of AMPH (0.25–2 mg/kg) using varying current levels and reinforcement schedules. Additional studies investigated the ability of nucleus accumbens (NAC) D1 and D2 receptor antagonists [SCH23390 (1–10μg); eticlopride (10μg); respectively] administration to regulate the AMPH potentiation of BSR performance. The study revealed selective breeding for the high alcohol preference phenotype was positively associated with AMPH's reward-potentiating effects on BSR. This relationship was more readily observed when the “cost” [i.e., work requirement] for the stimulation increased under an intermittent FR-6 schedule. AMPH's potentiating effects on BSR were regulated via D1, but not D2 dopamine (DA) receptors within the NAC. I suggest that a deficient DA system in HAD-1 rats may predispose/enhance their sensitivity to the AMPH potentiating effects on BSR. Because LAD-1 rats possess a greater level of DA, their reward circuitry may not be as sensitive to the AMPH-induced DA release in mesolimbic reward loci. I propose that common/overlapping neuronal mechanisms of which the NAC is a pivotal substrate may regulate increased sensitivity to alcohol and AMPH's reinforcing properties in HAD-1 rats.

Degree

Ph.D.

Advisors

June, Purdue University.

Subject Area

Psychobiology

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