Prazosin modulates the firing pattern of dopamine neurons in rat ventral tegmental area

Abstract

Previous studies have indicated a noradrenergic modulation of midbrain dopamine cell activity. The effects of systemic administration of the α 1-adrenoceptor antagonist prazosin and the α 2-antagonist idazoxan on midbrain dopamine cell firing were now studied with extracellular recording from single dopamine neurons in the ventral tegmental area of chloral hydrate-anaesthetized male rats. Prazosin (0.15–0.6 mg/kg i.v.) dose dependently decreased burst firing and regularized the firing pattern of dopamine neurons, while the firing rate was unaffected. The prazosin-induced effects were abolished by pretreatment with reserpine. Idazoxan (0.5–2.0 mg/kg i.v.) increased firing rate and burst firing and made the firing pattern less regular, probably by increasing adrenergic transmission via blockade of presynaptic α 2-adrenoceptors. The effects of idazoxan were blocked by prazosin. The present results indicate that noradrenergic neurons modulate the dopamine cell firing pattern via excitatory postsynaptic α 1-adrenoceptors. This mechanism might be involved in the pathogenesis and pharmacological treatment of schizophrenia.