Morphine-nicotine interaction in conditioned place preference in mice after chronic nicotine exposure.
Previously we found that morphine's effects on locomotor activity and brain dopamine metabolism were enhanced in mice after cessation of 7-week oral nicotine treatment. In the present experiments we show that such chronic nicotine exposure cross-sensitizes NMRI mice to the reinforcing effect of morphine in the conditioned place preference paradigm. The nicotine-treated mice developed conditioned place preference after being conditioned twice with morphine 5 mg/kg s.c. whereas in control mice a higher dose (10 mg/kg) of morphine was required. Since the reinforcing effect of morphine is mediated via micro-opioid receptors we used [3H]DAMGO autoradiography to study whether the number (B(max)) or affinity (K(D)) of mu-opioid receptors in the mouse brain are affected following chronic nicotine exposure. However, no changes were found in the number or affinity of micro-opioid receptors in any of the brain areas studied. Neither did we find alterations in the functional activity of mu-opioid receptors studied by [35S]GTPgammaS-binding. In conclusion, chronic oral nicotine treatment augments the reinforcing effects of morphine in mice, and this cross-sensitization does not seem to be mediated by micro-opioid receptors.
Vihavainen
Tanja
T
Division of Pharmacology and Toxicology, Faculty of Pharmacy, P.O. Box 56 (Viikinkaari 5 E), University of Helsinki, FI-00014, Finland. tanja.vihavainen@helsinki.fi
Piltonen
Marjo
M
Tuominen
Raimo K
RK
Korpi
Esa R
ER
Ahtee
Liisa
L
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D003216:Conditioning, Operant / Q000187:drug effects*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000187:drug effects
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009271:Naltrexone; D009538:Nicotine; D009020:Morphine