The effects of dopamine D3/D2 receptor agonists on intracranial self stimulation in the rat.
The effects of the dopamine D3/D2 receptor agonists quinpirole, quinelorane and (+/-)7-OH-DPAT [(+/-) 7-hydroxy-2(N,N-di-n-propylamino) tetralin] on intracranial self-stimulation (ICSS) were investigated. Rats implanted with bipolar electrodes into the lateral hypothalamus were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. Three measures of responding were calculated; the frequency at which responding was 50% of the maximum (M50), the asymptotic response rate and the total area under the curve (AUC) for each frequency sweep. Quinpirole (2.2-66.0 microg/kg SC) significantly increased M50 and reduced both asymptote and AUC. Quinelorane (0.25-79.0 microg/kg SC) had no significant effect on M50 values but significantly reduced both asymptote and AUC. (+/-)7-OH-DPAT (2.5-74.0 microg/kg) did not significantly affect any of the measures. The data show that low doses of quinpirole and quinelorane, but not (+/-)7-OH-DPAT, inhibit ICSS maintained by electrodes in the lateral hypothalamus. Either dopamine D2 or dopamine D3 receptor stimulation may play a role in mediating ICSS inhibition, but studies with more selective receptor agonists and antagonists are required to define the role of each receptor.
Hatcher
J P
JP
Neurosciences Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
Hagan
J J
JJ
D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D012653:Self Stimulation / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology
D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D011804:Quinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; C047726:quinelorane