Differential effects of cocaine on firing rate and pattern of dopamine neurons: role of alpha1 receptors and comparison with L-dopa and apomorphine.
Psychostimulants, including cocaine, have two opposing effects on dopamine (DA) neurons: a DA-mediated inhibition and a non-DA-mediated excitation. The latter, expressed as an increase in both firing rate and a slow oscillation (SO) in firing pattern, has been shown to require forebrain inputs to DA neurons and activation of adrenergic alpha(1) receptors. However, since the effect was observed when the DA-mediated inhibition was blocked by a D2 antagonist, it is uncertain whether the underlying mechanism also plays a role in cocaine's effects in normal animals where D2-like receptors are not blocked. This study showed that under such conditions, cocaine decreased firing rate and bursting without significantly inhibiting the SO in DA neurons recorded in the ventral tegmental area. Different from cocaine, l-dopa and apomorphine, two nonpsychostimulant DA agonists known to lack the alpha(1)-mediated excitatory effect, consistently inhibited all three measures of DA cell activity. Blockade of alpha(1) receptors by prazosin did not enhance cocaine's ability to inhibit firing rate and bursting, but it did enable cocaine to inhibit the SO. These results suggest that in control rats where D2-like receptors are not blocked, alpha(1) receptors play an important role in cocaine's effect on the SO but not in its effect on firing rate and bursting of DA neurons. The maintained SO after cocaine injection may reflect continued modulation of DA neurons by forebrain inputs, regulate the pattern of DA release, and provide a temporal structure for selection of synaptic inputs to DA neurons.
Zhou
Yan
Y
Neuropsychopharmacological Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 0651, USA.
Bunney
Bejamin S
BS
Shi
Wei-Xing
WX
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000502:physiology*
D015259:Dopamine Agents; D018340:Receptors, Adrenergic, alpha-1; D007980:Levodopa; D003042:Cocaine; D001058:Apomorphine; D004298:Dopamine