Comparison of the effects of nicotine and epibatidine given in combination with nomifensine on rotational behaviour in rats.
We studied the effects of nicotine and epibatidine on rotational behaviour in 6-hydroxydopamine-lesioned rats. The nicotinic agonists were given acutely and repeatedly either alone or in combination with a dopamine uptake inhibitor, nomifensine. Neither nicotine nor epibatidine alone produced acutely ipsilateral rotational behaviour in rats. However, when given repeatedly once a day for five days, nicotine (0.5 mg/kg) and epibatidine (0.6 microg/kg but not 3.0 microg/kg) induced ipsilateral rotations indicating sensitization of the nigrostriatal dopaminergic system to activation by repeated treatment with nicotinic agonists. Nomifensine (3 mg/kg) alone induced acutely ipsilateral rotations and the effect was enhanced after repeated administration of nomifensine. When the combination of nomifensine and nicotinic agonists was given acutely, the rotational effect of nomifensine was enhanced by nicotine (0.5 mg/kg) but not by either dose of epibatidine. When given repeatedly, nicotine and epibatidine 0.6 microg/kg tended to prolong whereas epibatidine 3.0 microg/kg tended to inhibit the enhanced rotational response to repeated nomifensine. The sensitization of the nigrostriatal dopaminergic pathway might be involved in the beneficial effects of nicotine in Parkinson's disease by allowing the remaining dopaminergic synapses to compensate for the functional deficiency of nigrostriatal pathway.
Janhunen
Sanna
S
Faculty of Pharmacy, Division of Pharmacology and Toxicology, University of Helsinki, P.O. Box 56, Viikinkaari 5, Helsinki FIN-00014, Finland.
Tuominen
Raimo K
RK
Ahtee
Liisa
L
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009627:Nomifensine / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018663:Adrenergic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D011725:Pyridines; D009627:Nomifensine; D009538:Nicotine; D016627:Oxidopamine; C082748:epibatidine