Dopamine infusion does not alter LH levels before or after chronic cocaine exposure in female rhesus monkeys.
Cocaine stimulates release of luteinizing hormone (LH) in preclinical and clinical studies but the contribution of the indirect dopamine agonist actions of cocaine to its effects on LH are unclear. In the present study, we examined the effects of exogenous dopamine infusions on LH release in drug-naive, normally cycling, female rhesus monkeys. All studies were conducted during the mid-follicular phase (cycle days 6-8). Three successive 80-min dopamine infusions (10 micrograms/kg/min, intravenous) were alternated with 20- or 40-min interruptions of dopamine infusions. There were no significant changes in LH during or following dopamine infusions. Predopamine baseline LH levels averaged 30 +/- 5.4 ng/ml. LH averaged 31.7 +/- 1.3 ng/ml during dopamine infusions and 31.4 +/- 1.3 ng/ml after dopamine infusions stopped. To determine whether chronic cocaine exposure influenced the effect of dopamine on LH, rhesus females were studied after more than 2 years of cocaine self-administration at an average dose of 6.5 +/- 0.2 mg/kg/day. LH averaged 27.3 +/- 3.3 ng/ml during baseline and 26.9 +/- 0.7 ng/ml and 26.1 +/- 0.7 ng/ml during dopamine infusions and interruptions, respectively. Similarly, during withdrawal from cocaine, baseline LH levels averaged 32.1 +/- 4.5 ng/ml, and LH did not change significantly during dopamine infusions (31.2 +/- 1.1 ng/ml) and infusion interruptions (32.1 +/- 1.1 ng/ml). Under the conditions of the present study, dopamine administration did not change LH levels in gonadally intact rhesus monkeys, and these findings are consistent with previous studies in ovariectomized rhesus females. However, these data are not consistent with clinical reports, and some possible implications of this species difference are discussed. Moreover, these data suggest that the stimulation of LH by cocaine may not be explained by its indirect dopamine agonist actions.
Mello
N K
NK
Endocrine Unit, McLean Hospital, Belmont, MA 02178, USA.
Mendelson
J H
JH
Kelly
M
M
Diaz-Migoyo
N
N
Sholar
J W
JW
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D007262:Infusions, Intravenous; D007986:Luteinizing Hormone / Q000097:blood*; D008253:Macaca mulatta; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D007986:Luteinizing Hormone; D003042:Cocaine; D004298:Dopamine