Differential involvement of dopamine D1 receptors in morphine- and lithium-conditioned saccharin avoidance

Conditioned saccharin avoidance (CSA) can be produced when either lithium chloride (LiCl) or a reinforcing drug, such as morphine, is administered following exposure to the taste of saccharin. In this study we investigated the involvement of dopamine (DA) transmission in the acquisition of morphine and LiCl-CSA. CSA was evaluated in a two-bottle choice paradigm with two conditioning pairings between saccharin and morphine or LiCl as unconditioned stimulus (US). Morphine hydrochloride (7.5 mg/kg s.c.) or LiCl (40 mg/kg i.p.), administered 45 and 120′ respectively after saccharin-drinking session, induced strong CSA. The DA D1 receptor antagonist, SCH 39166 (0.1 mg/kg s.c.), impaired morphine-CSA if administered 15′ and, to a lesser extent, 30′ but not 45′ before the drug (i.e immediately after saccharin drinking). In contrast SCH 39166 reduced LiCl-CSA when administered 45′ before the drug and even more so when administered 105′ before LiCl i.e. immediately after saccharin drinking. Therefore SCH 39166 impaired morphine-CSA when given shortly before the drug, while it impaired LiCl-CSA when given shortly after saccharin. Raclopride, a specific antagonist of D2 receptors, failed to affect LiCl- and morphine-CSA. These results are consistent with the idea that DA, acting on D1 receptors, plays a differential role in morphine- and LiCl-CSA. In LiCl-CSA DA is necessary for the processing (consolidation) of the short-term memory trace of the saccharin taste to be associated with the lithium-induced aversive state, while in morphine CSA contributes to mediate the appetitive properties of the drug.