Cueing effects of amphetamine and LSD: Elicitation by direct microinjection of the drugs into the nucleus accumbens

Two groups of rats were trained to discriminate either d-amphetamine sulphate (AMPH; 1 mg/kg) or d-lysergic acid diethylamide bitartrate (LSD; 0.16 mg/kg). Microinjection of AMPH into the nucleus accumbens elicited a cueing effect which was similar to that of systemically administered AMPH in AMPH-trained animals (ED50 was 0.24 micrograms). Co-injection of (-)-sulpiride (50 or 100 ng) into the accumbens antagonized the effect of a fixed dose of AMPH (1 microgram) which, alone, produced 76% of the systemic AMPH cue effect. Microinjections of AMPH (1-5 micrograms) into either the anterior dorsomedial or the anterior ventrolateral striatum failed to elicit the cueing effect of AMPH. In LSD-trained animals a dose of 1 microgram LSD injected into the accumbens produced 84% of the systemic cueing effect of LSD. These results suggest that dopamine (DA) receptors in the nucleus accumbens are involved in AMPH discrimination. Furthermore, since both classical and atypical antipsychotic drugs block the AMPH cue, the results provide indirect evidence for involvement of mesolimbic DA in antipsychotic drug action.