Chronic L-DOPA-pretreatment of rats: an electrophysiological and biochemical study in the basal ganglia.
Treatment of rats with L-DOPA (251.25 mg as the methyl ester HCl/kg) plus benserazide (B, 50 mg/kg) (L-DOPA+B), twice daily (i.p.) for 5 days or 12 days resulted in the dopamine (DA) neurons of the substantia nigra pars compacta becoming subsensitive to the rate-depressing effects of D-amphetamine (i.v.) 16 to 24 h after the last chronic drug dose. In contrast, pretreated rats were significantly less sensitive than control rats to the rate depressant effects of apomorphine (i.v.) after 12, but not 5 days of L-DOPA+B-pretreatment. After 5, but not 12 days of L-DOPA+B-pretreatment, a significant increase in the number of spontaneously active DA neurons was noted in the substantia nigra pars compacta. Caudate tyrosine hydroxylase was examined and a significant increase in apparent Vmax was noted after 5 days of L-DOPA+B, with no apparent change being noted in Km for cofactor. At this time, no change was noted in caudate DA or HVA concentrations. Several distinct processes may be occurring in response to the L-DOPA+B-pretreatment: (1) the DA autoreceptors located on cell bodies in the substantia nigra have become subsensitive after 12 days of L-DOPA+B-pretreatment; (2) the subsensitivity to D-amphetamine seen after both chronic schedules is probably unrelated to the subsensitive DA autoreceptors and may depend upon homeostatic alterations in neurotransmitter systems other than those utilising DA; (3) the activation of tyrosine hydroxylase may be a reflection of the increase in the number of spontaneously active units.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001479:Basal Ganglia / Q000187:drug effects*; D001545:Benserazide / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D001545:Benserazide; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine; D006719:Homovanillic Acid