Pharmacological evidence for common mechanisms underlying the effects of neurotensin and neuroleptics on in vivo dopamine efflux in the rat nucleus accumbens.
The effects of the neuropeptide neurotensin and the typical neuroleptic haloperidol on dopamine efflux were compared in the posteromedial nucleus accumbens of the chloral hydrate-anesthetized rat using in vivo chronoamperometry. Both neurotensin and haloperidol administration elicited an immediate increase in dopamine efflux in the nucleus accumbens. Gamma-hydroxybutyric acid lactone, an agent known to block impulse flow in dopamine neurons, either prevented when given before neurotensin or reversed neurotensin-induced increases in accumbens dopamine efflux. Haloperidol-induced increases in accumbens dopamine efflux were similarly affected by gamma-hydroxybutyric acid lactone. The dopamine receptor agonist apomorphine reversed neurotensin- and haloperidol-induced increases in dopamine efflux. Amphetamine, administered during the peak dopamine stimulatory effects induced by neurotensin or haloperidol, resulted in increases above baseline which were significantly greater than the effects of amphetamine alone. These combined drug treatment effects on baseline dopamine efflux were additive, indicating that the effects of amphetamine were not potentiated by neurotensin or haloperidol pretreatments. These in vivo results suggest that neurotensin and haloperidol may augment dopamine efflux in the nucleus accumbens via common mechanisms of action which may involve activation of mesotelencephalic dopamine neuronal firing. The inability of neurotensin to block amphetamine-induced efflux in the nucleus accumbens further suggests that neurotensin blockade of amphetamine-elicited locomotor activity is mediated by an action of neurotensin postsynaptic to dopamine nerve terminals in the nucleus accumbens.
Blaha
C D
CD
Department of Psychology, University of British Columbia, Vancouver, Canada.
Phillips
A G
AG
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods; D006220:Haloperidol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology
D009496:Neurotensin; D013779:Tetrodotoxin; D006220:Haloperidol; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine