Differential ability of D1 and D2 dopamine receptor agonists to induce and modulate expression and reinstatement of cocaine place preference in rats

Abstract

Rationale: D1-Like agonists are self-administered by drug-naive animals, whereas D2-like agonists reinstate cocaine-seeking behavior, but the rewarding and reinstating effects of D1- and D2-like agonists in pavlovian-based conditioned place preference are equivocal.

Objective: To compare the ability of D1 and D2 agonists to produce conditioned place preference with their modulation of expression and reinstatement of an established cocaine place preference.

Methods: Using an unbiased procedure, we measured the place preference induced by the D1 receptor agonist SKF 81297 and the D2/D3 receptor agonist quinpirole in drug-naive or cocaine-exposed rats. The rewarding effects of the D1 agonists SKF 82958, ABT-431, A-77636, and the D2/D3 receptor agonist 7-OH-DPAT were also tested. Additionally, we tested the ability of SKF 81297 and quinpirole to modulate expression and reinstatement of an established cocaine place preference.

Results: The D1 receptor agonists SKF 81297, SKF 82958, and ABT-431 produced dose-dependent conditioned place preferences, whereas A-77636 produced only place aversion, and the D2/D3 agonists quinpirole and 7-OH-DPAT were without effect in drug naive rats. In cocaine-treated rats, SKF-81297-induced place preference was reduced, whereas quinpirole-induced place preference was revealed. Pretreatment using either D1 or D2/D3 agonists blocked expression of an established cocaine place preference, but only the D1 agonist SKF 81297 and cocaine dose-dependently reinstated an extinguished cocaine place preference, whereas the D2/D3 agonist quinpirole induced place aversion but failed to alter cocaine-induced reinstatement.

Conclusions: D1, but not D2/D3, agonists mediate rewarding effects and reinstatement of cocaine place preference, but the reinstating effects differ markedly from self-administration paradigms.