Post‐Session Administration of Selective Dopamine D3 Receptor Antagonists Disrupts Water‐Reinforced Operant Responding: Involvement of Cholinergic Receptors

Abstract

Previous research has shown that post‐session administration of dopamine receptor agonists disrupts fluid‐reinforced operant responding. The present study examined the ability of post‐session administration of dopamine receptor antagonists to disrupt water‐reinforced responding. Post‐session administration of the selective D3 receptor (D3R) antagonists, PG01037 and SB‐277011A, caused progressive, monotonic declines in responding across sessions. These inter‐session declines were paralleled by progressive intra‐session response decrements. These effects were not observed when PG01037 was given on a quasi‐random schedule designed to minimize the contingencies between the session and drug administration. Responding was not disrupted by post‐session administration of the non‐selective D2‐like receptor antagonist, haloperidol; the selective D2 receptor antagonist, L‐741,626; or the D1‐like receptor antagonist, SCH23390. Thus, these effects are specific to D3R‐selective antagonists. This ability of D3R antagonists to disrupt responding may be related to their effects on cholinergic transmission: the disruptions caused by post‐session PG01037, but not those caused by post‐session administration of the D3R preferring agonist, pramipexole, are significantly attenuated by pretreatment with scopolamine. Support: USPHS/NIDA grant R01 DA020669 and an NSF Graduate Research Fellowship.