Rapid desensitization of presynaptic dopamine autoreceptors during exposure to exogenous dopamine.
When nomifensine is employed to inhibit neuronal uptake, exposure to dopamine (DA) (0.1-0.3 microM) or apomorphine (0.01-0.1 microM) inhibited, in a concentration-dependent manner, the electrically evoked release of [3H]dopamine from slices of the rabbit caudate nucleus. Apomorphine inhibited transmitter release independently of the time of exposure to the drug (6-32 min). On the other hand, the inhibitory effect of exogenous dopamine occurred only if a short period (4-12 min) of exposure was employed. In studies on the electrically evoked release of [3H]acetylcholine in slices of the rabbit caudate nucleus there was no evidence for desensitization to apomorphine or exogenous dopamine at the level of the dopamine receptors that inhibit [3H]acetylcholine release. These results indicate that the dopamine autoreceptors modulating [3H]dopamine release in the caudate nucleus become subsensitive after a few minutes of exposure to exogenous dopamine. This effect does not occur at the level of the dopamine receptors which inhibit the release of [3H]acetylcholine.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D004361:Drug Tolerance; D004558:Electric Stimulation; D005246:Feedback; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D011817:Rabbits; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors
D011954:Receptors, Dopamine; D009627:Nomifensine; D012110:Reserpine; D001058:Apomorphine; D000109:Acetylcholine; D004298:Dopamine