Effects of acute and chronic cocaine on the activity of tuberoinfundibular dopamine neurons in the rat.
We investigated the effects of acute and chronic cocaine on dopamine (DA) synthesis in tuberoinfundibular dopamine (TIDA) neurons by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA) in the median eminence (ME). Cocaine-induced prolactin (PRL) responses were evaluated for comparison. Acute cocaine inhibited DA synthesis in the ME and decreased circulating PRL. Chronic cocaine did not alter basal DOPA levels in TIDA nerve terminals or PRL levels in plasma. After repeated cocaine injections, cocaine's inhibitory effect on DA synthesis was abolished in the ME while the PRL response to drug was unchanged. These results suggest that TIDA neurons become tolerant to cocaine-induced suppression of DA synthesis after chronic cocaine exposure, but the altered sensitivity of TIDA neurons is not revealed by plasma PRL measures.
Clinical Psychopharmacology Section, National Institute on Drug Abuse, Addiction Research Center, Baltimore MD 21224.
M H
MH
Baumann
R B
RB
Rothman
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis* / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004295:Dihydroxyphenylalanine; D011388:Prolactin; D003042:Cocaine; D004298:Dopamine