Central nervous system stimulants: neuropharmacological mechanisms

The mechanisms underlying CNS-stimulant drug discrimination are discussed. Although different doses of CNS stimulants may produce qualitatively different cues, it appears that a relatively low dose of d-amphetamine (e.g., 1 mg/kg) elicits a "general" CNS-stimulant cue. Presynaptically, this cue may primarily depend on release of endogenous dopamine whereas inhibition of dopamine reuptake, per se, is insufficient to elicit the cue. Postsynaptically, the involvement of both dopamine D-1 and D-2 receptors is implicated. Furthermore, in the drug discrimination situation, D-1/D-2 receptors may be coupled differently than in dopamine-dependent locomotor activation. Anatomically, CNS-stimulant drug discrimination may depend primarily on mesolimbic dopamine systems.