Prominent role of alpha3/alpha6beta2* nAChRs in regulating evoked dopamine release in primate putamen: effect of long-term nicotine treatment.
Brain dopaminergic systems are critical in motor control as evidenced by findings that their disruption results in movement disorders such as Parkinson's disease. Nicotinic acetylcholine receptor (nAChR) activation plays an important role in regulating striatal dopaminergic function. Rodent studies show that short-term nicotine exposure influences stimulated striatal dopamine release with responsiveness dependent on neuronal activity. However, studies have not yet been done in nonhuman primates, nor has work been done to evaluate the effect of long-term nicotine exposure, which is relevant for therapies for chronic neurological disorders. Here, we used voltammetry to assess the role of nAChRs on evoked dopamine release from monkey putamen slices. In both ventral and dorsal putamen, alpha3/alpha6beta2(*) nAChRs regulated > or =80% of non-burst- (single pulse) nAChR-modulated dopamine release, and alpha4beta2(*) nAChRs regulated the remainder. Similar results were observed with burst-firing in ventral but not dorsal putamen, indicating that nAChR-modulated effects on release depend on the subregion and firing frequency. Next, we investigated the consequence of long-term nicotine exposure via the drinking water on nAChR-modulated responsiveness. Nicotine treatment altered both non-burst- and burst-stimulated dopamine release in ventral but not dorsal putamen. Altogether, these data support a predominant role for alpha3/alpha6beta2(*) nAChRs in the regulation of evoked dopamine release in nonhuman primate putamen. They also show that long-term nicotine treatment selectively modifies nAChR-modulated release in distinct striatal subregions. These findings have implications for the development of treatments for addiction and neurological disorders with nAChR dysfunction.
Perez
Xiomara A
XA
The Parkinson's Institute, Sunnyvale, CA 94085, USA.
O'Leary
Kathryn T
KT
Parameswaran
Neeraja
N
McIntosh
J Michael
JM
Quik
Maryka
M
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009538:Nicotine / Q000008:administration & dosage*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000502:physiology*; D012453:Saimiri; D013997:Time Factors
D011978:Receptors, Nicotinic; C559463:alpha6beta2 nicotinic acetylcholine receptor; C419362:nicotinic receptor alpha3beta2; D009538:Nicotine; D004298:Dopamine