Psychostimulants induce low-frequency oscillations in the firing activity of dopamine neurons.
The reinforcing properties of psychostimulants depend critically on their effects on dopamine (DA) neurons in the ventral tegmental area (VTA). Using in vivo single unit recording in rats and spectral analysis, this study presents evidence for a new, non-DA-mediated effect of psychostimulants on VTA DA neurons. Thus, as previously observed with D-amphetamine, all psychostimulants tested, including cocaine, methamphetamine, and methylphenidate, had two opposing effects on firing rate of DA neurons: a DA-mediated inhibition and a non-DA-mediated excitation. The latter effect was normally masked by the DA-mediated inhibition and was revealed when the inhibition was blocked by a DA antagonist. Using spectral analysis, this study further showed that during psychostimulant-induced excitation, DA cells exhibited not only an increase in firing rate and bursting but also a low-frequency rhythmic oscillation (0.5-1.5 Hz) in their firing activity. The oscillatory response was unique to psychostimulants since it was not observed with the GABA(A) agonist muscimol, which also increased DA cell firing, and not mimicked by the nonpsychostimulant DA agonist L-dopa. Results further suggest that the effect requires activation of adrenergic alpha1 receptors and depends on intact forebrain inputs to DA neurons. Further understanding of this novel effect may provide important insights into both the mechanism of action of psychostimulants and the neuronal circuitry that controls the activity of DA neurons in the brain.
Shi
Wei-Xing
WX
Neuropsychopharmacological Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA. wei-xing.shi@yale.edu
Pun
Chen-Lun
CL
Zhou
Yan
Y
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D007839:Functional Laterality / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D010507:Periodicity; D016548:Prosencephalon / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013057:Spectrum Analysis / Q000379:methods; D017557:Ventral Tegmental Area / Q000166:cytology
D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D018755:GABA Agonists; D009118:Muscimol; D004298:Dopamine