Review on the relationship between nicotinic acetylcholine receptors and dopaminergic neurotransmission in the central nervous system--dopa is an endogenous neuroactive substance.
L-3,4-Dihydroxyphenylalanine (DOPA) is believed to be an inert precursor for dopamine (DA). Contrary, transmitter-like endogenous DOPA is released from in vitro and in vivo striata: DOPA is released by neuronal activities under physiological conditions from striata of conscious rats. Furthermore, exogenous nanomolar DOPA itself produces an in vitro presynaptic response to facilitate the catecholamine release. An in vivo postsynaptic depressor response is elicited by DOPA microinjected into the nucleus tractus solitarii. These responses are antagonized by L-DOPA methyl ester, a competitive DOPA antagonist. In striata, DOPA is an endogenous potentiator for presynaptic beta-adrenoceptors to facilitate the DA release and also probably for postsynaptic D2-receptors to increase locomotor activities. Nicotine releases DA and transmitter-like DOPA in vitro and in vivo striata. Nicotine (0.1-1.0 mg/kg, sc) dose-dependently increases locomotor activities. This increase is stereoselective and mecamylamine (1.0 mg/kg, sc)-sensitive but not antagonized by L-DOPA methyl ester (200 micrograms, ivt). Then, a selective low ip dose of alpha-methyl-p-tyrosine (alpha-MPT) to inhibit the basal release of DOPA without decreasing the basal release of DA was explored in vivo striata: it was 3 mg/kg. Pretreatment with this dose did inhibit the nicotine-induced increases in locomotor activities. This result suggests that endogenously released DOPA is in part relevant to nicotine-induced behavior in rats.
Misu
Y
Y
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Nakamura
S
S
Goshima
Y
Y
Yue
J L
JL
Miyamae
T
T
Kubo
T
T
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D007980:Levodopa / Q000031:analogs & derivatives / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic; D013569:Synapses / Q000187:drug effects
D002395:Catecholamines; D011978:Receptors, Nicotinic; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D009538:Nicotine; C035420:levodopa methyl ester