Cross-tolerance in drug response and differential changes in central nicotinic and N-methyl-D-aspartate receptor binding following chronic treatment with either (+)- or (-)-nicotine.
The present study compared the effects of chronic treatment (21 days) with (+)-nicotine and (-)-nicotine on exploratory behaviours and body temperature in rats. Chronic treatment with either (+)- or (-)-nicotine induced tolerance in exploratory behaviours. A cross-tolerance between the two stereoisomers was also observed. Body temperature was differentially affected by chronic (+)- and (-)-nicotine, but cross-tolerance was still observed. In addition, nicotinic acetylcholine receptor (nAChR) and N-methyl-D-aspartate (NMDA) receptor binding in rats treated with (+)- and (-)-nicotine were measured by receptor autoradiography. Chronic treatment with (+)- and (-)-nicotine significantly increased nAChR binding in different brain regions. Furthermore, significant differences in the induction of nAChR binding by chronic (+)- and (-)-nicotine were detected in several brain regions. Chronic treatment with (+)-nicotine significantly increased NMDA receptor binding in the CA1 region of the hippocampus. However, (-)-nicotine had no effect on NMDA receptor binding in any of the regions analysed. These results demonstrate differences between chronic treatment with (+)- and (-)-nicotine in physiological responses such as body temperature and biochemical changes such as changes in nAChRs and NMDA receptor binding, although a cross-tolerance between the two enantiomers in behaviour and body temperature is also observed.
Wall
A
A
Division of Molecular Neuropharmacology, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Karolinska Institutet, Huddinge University Hospital, B84, S-141 86 Huddinge, Sweden.
Gong
Z H
ZH
Johnson
A E
AE
Meyerson
B
B
Zhang
X
X
D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013237:Stereoisomerism; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D016291:Dizocilpine Maleate; D009538:Nicotine