Nicotine blocks quinpirole-induced behavior in rats: psychiatric implications.
OBJECTIVE
Because of known and imputed roles of dopaminergic and nicotinic cholinergic systems in a variety of neurological and neuropsychiatric disorders, combined neurochemical and behavioral methods assessments were made to study the intermodulatory roles of these neurochemical systems.


METHODS
Rats were treated daily during postnatal ontogeny with the dopamine D2/D) agonist, quinpirole (QNP) HCl (1.0 mg/kg/day), for the first 3 weeks from birth. This priming process replicated previous findings of behavioral sensitization, manifested as hyperlocomotion, increased paw treading with jumping, and increased yawning.


RESULTS
All effects were partially or totally blocked by acute treatment with nicotine (0.3 mg/kg, i.p.). The effects of nicotine, in turn, were partially or totally blocked by the nicotinic antagonist, mecamylamine (1.0 mg/kg, i.p.). In concert with these behavioral actions, QNP-primed rats displayed greater binding of [3H]cytisine in midbrain and cerebellum and greater [125I]alpha-bungarotoxin binding in hippocampus and striatum.


CONCLUSIONS
Accordingly, these selective ligands for alpha4beta2 and alpha7 nicotinic receptors, respectively, demonstrate that nicotinic receptors are altered by dopamine D2/D3 agonist treatment of rats with primed dopamine receptors. We propose that nicotinic agonists may have a therapeutic benefit in behavioral disorders brought about by central dopaminergic imbalance.
Tizabi
Y
Y
Department of Pharmacology, College of Medicine, Howard University, 520W Street N.W., Washington, DC 20059, USA. ytizabi@howard.edu
Copeland
R L
RL
Brus
R
R
Kostrzewa
R M
RM
D000470:Alkaloids / Q000378:metabolism; D000818:Animals; D001392:Azocines; D001522:Behavior, Animal / Q000187:drug effects*; D002038:Bungarotoxins / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000627:therapeutic use; D011807:Quinolizines; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology; D015000:Yawning / Q000187:drug effects; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D002038:Bungarotoxins; D018491:Dopamine Agonists; D008464:Mecamylamine; D009538:Nicotine; D018722:Nicotinic Agonists; D011807:Quinolizines; D019257:Quinpirole; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids