Facilitation of conditioned taste aversion learning by systemic amphetamine: role of nucleus accumbens shell dopamine D1 receptors

The role of dopamine (DA) in associative learning was studied in a conditioned taste aversion (CTA) paradigm with sucrose as the conditioned stimulus (CS) and intraperitoneal lithium chloride as the unconditioned stimulus (US). Drinking on trial of a 15% sucrose solution followed 1 h later by lithium chloride (20 or 40 mg/kg i.p.) resulted in mild CTA, as shown by reduction of drinking of the sucrose solution 24 h later. Amphetamine sulphate (0.125, 0.25, 0.50 and 1.0 mg/kg s.c.), administered on trial 5 min after sucrose drinking, facilitated CTA with maximal effects at 0.25 mg/kg s.c. Amphetamine given in the absence of lithium or 45 min after sucrose did not affect sucrose intake. The DA D1 receptor antagonist SCH 39166, administered before amphetamine either systemically (0.0125 mg/kg s.c.) or in the nucleus accumbens shell (NAc; 0.025 micro g/ micro L on each side) prevented the facilitation of CTA induced by amphetamine. It is concluded that amphetamine facilitates CTA learning by strengthening the consolidation of gustatory short-term memory via D1 receptors of the NAc shell.