Context-controlled nicotine-induced changes in the labeling of serotonin (5-HT)2A and 5-HT2C receptors in the rat brain.
BACKGROUND
We have previously demonstrated that serotonin (5-HT)2A and 5-HT2C receptor ligands modulate the sensitizing effects of nicotine. In the present study we used male rats to verify the hypothesis that the binding pattern of 5-HT2A and 5-HT2C receptors in the brain is altered by chronic nicotine treatment in different environments.


METHODS
Rats were given repeatedly vehicle or nicotine in different sensitizing regimens (home or experimental cages). On day 10, animals were challenged with nicotine (expression of nicotine sensitization) or vehicle in either home or experimental cages, and were sacrificed immediately after the experiment.


RESULTS
Repeated treatment with nicotine in home cages evoked significant increases in [(3)H]ketanserin binding to 5-HT2A receptors in the prefrontal cortex, striatal subregions and ventral tegmental area as well as reductions in [(3)H]mesulergine binding to 5-HT2C receptors in subregions of the prefrontal cortex. In contrast, nicotine paired with environmental context produced robust increases in 5-HT2A receptor labeling in the infralimbic cortex and decreased [(3)H]ketanserin binding in striatal subregions and ventral tegmental area; 5-HT2C receptor labeling in the prefrontal cortex fell.


CONCLUSIONS
The present data indicate that chronic nicotine administration in home cages induces bi-directional neuroplastic changes within 5-HT2A and 5-HT2C receptors in the prefrontal cortex. Pairing the nicotine with environmental context potentiates the neuroplastic response in the latter region and evokes opposite changes in 5-HT2A receptor binding in striatal and tegmental regions compared with nicotine administered in the absence of the context, indicating a modulatory role of environmental context in the expression of nicotine-induced sensitization.
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: zaniew@if-pan.krakow.pl.
Magdalena
M
Zaniewska
Brains-On-Line, Groningen, The Netherlands.
Andrew C
AC
McCreary
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Karolina
K
Wydra
Laboratory of Biochemical Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Agata
A
Faron-Górecka
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Małgorzata
M
Filip
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D013194:Staining and Labeling / Q000379:methods
D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D009538:Nicotine
Context-dependent sensitization; Nicotine; Quantitative 5-HT(2) receptor autoradiography; Rat