Effect of quinpirole on striatal dopamine release and locomotor activity in nicotine-treated mice.
The effect of chronic oral nicotine treatment which in its intermittent delivery resembles human smoking was studied on the sensitivity of dopamine autoreceptors in mice. On the 50th day of nicotine administration in the drinking water or after 23-25 h withdrawal quinpirole (D2/D3 agonist, 0.01-0.1 mg/kg s.c.) was given, and accumbal and dorsal striatal dopamine outflow, locomotor activity and body temperature were measured. Dorsal striatal extracellular dopamine concentration and locomotor activity were found to be elevated during nicotine administration. Chronic nicotine did not alter the effects of small, autoreceptor preferring doses of quinpirole on accumbal or dorsal striatal dopamine, locomotor activity or body temperature. However, quinpirole's locomotor activity reducing effect was slightly diminished in mice treated repeatedly with nicotine (0.4 mg/kg twice daily for 10 days s.c.). Thus, although repeated nicotine treatment for 5-14 days decreases dopamine autoreceptor sensitivity, after long-term oral nicotine treatment such a decrease is not seen. Thus, the changes occurring in the sensitivity of D2-like dopamine receptors probably play a minor role in regulating the dopaminergic transmission during long-term nicotine administration.
Tammimäki
Anne
A
Division of Pharmacology and Toxicology, Faculty of Pharmacy, P.O. Box 56, FIN-00014 University of Helsinki, Finland.
Pietilä
Kirsi
K
Raattamaa
Helena
H
Ahtee
Liisa
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology*; D013997:Time Factors
D018491:Dopamine Agonists; D005731:Ganglionic Stimulants; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D009538:Nicotine; D004298:Dopamine; D006719:Homovanillic Acid