Activation of postsynaptic striatal dopamine receptors, monitored by efflux of cAMP in vivo.
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.
Hutson
P H
PH
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
Suman-Chauhan
N
N
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
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