Prazosin modulates the firing pattern of dopamine neurons in rat ventral tegmental area.
Previous studies have indicated a noradrenergic modulation of midbrain dopamine cell activity. The effects of systemic administration of the alpha 1-adrenoceptor antagonist prazosin and the alpha 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 alpha 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 alpha 1-adrenoceptors. This mechanism might be involved in the pathogenesis and pharmacological treatment of schizophrenia.
Grenhoff
J
J
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Svensson
T H
TH
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004146:Dioxanes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013681:Tegmentum Mesencephali / Q000166:cytology* / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D012110:Reserpine; D004298:Dopamine; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan