Evidence for the involvement of central dopaminergic receptors in the acute and chronic effects induced by barbiturates.
There is close agreement in the literature concerning the effect of specific and directly acting dopaminergic (DA) agonists and antagonists on acute barbiturate-induced responses; with DA agonists inhibiting and DA agonists potentiating these responses. On the other hand, there are presently no studies (and hence no evidence) regarding the effects of direct and specific alterations of DA receptor arousal on chronic barbiturate-induced tolerance or withdrawal. Concerning the effect of acute barbiturate administration on central dopaminergic responses; while some studies report no effect, there is some evidence that barbiturates block DA reuptake after their acute administration. This is consistent with and may explain findings that these drugs also decrease striatal DA turnover acutely, decrease DA concentration in synaptosomes, and decrease postsynaptic DA receptor arousal. In noting the potentiation of acute barbiturate-induced responses elicited by DA antagonists, it is interesting to observe that barbiturates and DA antagonists both apparently decrease receptor sensitivity and inhibit DA reuptake presynaptically. Moreover, the supersensitivity to DA agonists induced by chronic DA antagonist administration can be potentiated by barbiturates. Thus, barbiturates appear to block the arousal of postsynaptic DA receptors, though probably not those coupled to adenylate cyclase and, unlike neuroleptics, indirectly. It is likely that the inhibitory effect on DA receptor arousal exerted by barbiturates accounts for at least some of the central effects produced by these drugs.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D002746:Chlorpromazine / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D004361:Drug Tolerance; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage; D006801:Humans; D006892:Hydroxydopamines / Q000008:administration & dosage; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010868:Pimozide / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
D001463:Barbiturates; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D010868:Pimozide; D016627:Oxidopamine; D000262:Adenylyl Cyclases; D006220:Haloperidol; D002746:Chlorpromazine; D004298:Dopamine; D009638:Norepinephrine