Lack of changes in cortical [3H]-muscimol binding in rats sensitized to nicotine-induced enhancement of dopamine metabolism.
It was proposed that chronic nicotine treatment may induce adaptive changes in GABAA receptors, thus leading to the attenuation of a GABAergic inhibition of dopaminergic neurons. This putative mechanism might underlie the sensitization to nicotine-induced increase in locomotor activity and dopamine metabolism; i.e. phenomena highly significant to the dependence-producing effects of this psychostimulant. To test this hypothesis, in the present study we have analyzed the influence of acute and repeated treatment of rats with nicotine on the binding of a highly selective and competitive GABAA receptor agonist, [3H]-muscimol. The binding was investigated by autoradiography in different brain cortical structures. It was found that nicotine given at the dose stimulating locomotor activity (0.6 mg/kg, sc), markedly increased striatal HVA concentration in the group of animals chronically pretreated (for 6 days) with this psychostimulant. Neither acute nor repeated nicotine administration changed in a significant way the [3H]-muscimol binding to brain cortical structures. Thus, the hypothesis about the role of adaptive changes in GABAA receptors in the enhancement of the biochemical and behavioral effects of nicotine was not confirmed.
Sienkiewicz-Jarosz
Halina
H
Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego 9, PL 02-957 Warszawa, Poland.
Członkowska
Agnieszka I
AI
Lehner
Małgorzata
M
Maciejak
Piotr
P
Siemiatkowski
Marek
M
Szyndler
Janusz
J
Wisłowska
Aleksandra
A
Zienowicz
Małgorzata
M
Bidziński
Andrzej
A
Kostowski
Wojciech
W
Płaźnik
Adam
A
D000818:Animals; D001345:Autoradiography; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000697:Central Nervous System Stimulants; D058785:GABA-A Receptor Agonists; D009118:Muscimol; D009538:Nicotine; D004298:Dopamine