Animal models of amphetamine psychosis: neurotransmitter release from rat brain slices

As animal models of psychosis, adult rats were exposed to different types of treatment with amphetamine: (1) subcutaneous implantation with osmotic minipumps or (2) daily intraperitoneal injections for 7 days and (3) one single amphetamine injection. Continuous administration caused tolerance, intermittent injections sensitization and the acute injection a behavioral arousal with stereotypes. All amphetamine treatments diminished the potassium-stimulated (50 mM) release of preloaded labelled dopamine from superfused striatal and frontal cortical slices in vitro. Only acute amphetamine enhanced the release of D-aspartate, an analogue of L-glutamate from frontal cortical slices. The results indicate that amphetamine profoundly affects the brain dopaminergic systems but less the glutamatergic systems. Amphetamine systematically enhanced the release of gamma-aminobutyrate (GABA) from striatal slices, but otherwise the GABAergic systems seem to be more sensitive to handling stress than to the administration of amphetamine. Besides dopaminergic mechanisms other interacting systems must thus be taken into account to explain behavioral responses to amphetamine.