A role for dopamine D1 receptors of the nucleus accumbens shell in conditioned taste aversion learning

The involvement of dopamine (DA) in conditioned taste aversion (CTA) learni ng was studied with saccharin or sucrose as the conditioned stimulus (CS) a nd intraperitoneal lithium as the unconditioned stimulus (US). The dopamine D-1 antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydr o-1H-3-benzazepine hydrochloride (SCH 23390) (12.5-50 mug/kg, s.c.), given 5 min after the CS, impaired the acquisition of CTA in a paradigm consistin g of three or a single CS-lithium association. SCH 23390 failed to impair C TA acquisition given 45 min after, 30 min before, or right before the CS. ( -)-trans- 6,7,7a, 8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5a-benzo-(D )-naphtho(2,1b) azepine (SCH 39166) (12.5-50.0 mug/kg, s.c), a SCH 23390 an alog that does not bind to 5HT(2) receptors, also impaired CTA. No signific ant impairment of CTA was obtained after administration of the specific D-2 /D-3 antagonist raclopride (100 and 300 mug/kg, s.c.). The ability of SCH 2 3390 to impair CTA learning was confirmed by its ability to reduce the cond itional aversive reactions to a gustatory CS (sweet chocolate) as estimated in a taste reactivity paradigm. SCH 39166 impaired CTA also when infused i n the nucleus accumbens (NAc) shell 5 min after the CS. No impairment was o btained from the NAc core or from the bed nucleus stria terminalis. The res ults indicate that D-1 receptor blockade impairs CTA learning by disrupting the formation of a short-term memory trace of the gustatory CS and that en dogenous dopamine acting on D-1 receptors in the NAc shell plays a role in short-term memory processes related to associative gustatory learning.