title: Activation of postsynaptic striatal dopamine receptors, monitored by efflux of cAMP in vivo.
abstract: Intracerebral dialysis was used to monitor the change of extracellular concentration of striatal cAMP in rats anaesthetised with chloral hydrate. Forskolin (1-10 microM), an activator of adenylate cyclase, caused a concentration-dependent increase in efflux of cAMP, which was decreased by (+)PHNO (10 microM), an effect probably mediated by D2 sites, since (-)-sulpiride, a D2 receptor antagonist prevented these effects. Dopamine (1-100 microM) also increased the efflux of cAMP but only when the activity of monoamine oxidase and reuptake of dopamine were concomitantly blocked. The D1 receptor agonist SKF 38393 (1-100 microM) caused a concentration-dependent increase in efflux of cAMP, which was blocked by the D1 receptor antagonist SCH 23390 (1-100 microM), but was unaffected by the D2 receptor antagonist sulpiride (10 microM) or by depletion of the concentration of striatal dopamine after pretreatment with 6-hydroxydopamine. Taken together, these results indicate that intracerebral dialysis may be used to monitor the interaction of drugs with post-synaptic dopamine receptors in vivo.
authors.affiliation: Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
authors.forename: P H
authors.initials: PH
authors.lastname: Hutson
authors.forename: N
authors.initials: N
authors.lastname: Suman-Chauhan
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D013569:Synapses / Q000502:physiology
chemical_list: D001552:Benzazepines; D015259:Dopamine Agents; D006892:Hydroxydopamines; D010078:Oxazines; D011954:Receptors, Dopamine; D005576:Colforsin; C042631:naxagolide; D013469:Sulpiride; D016627:Oxidopamine; D000242:Cyclic AMP; D003891:Desipramine