Monoaminergic drugs and directly observable signs of LAAM withdrawal in rhesus monkeys.
Monoaminergic ligands modified a naltrexone discriminative stimulus in rhesus monkeys dependent on 2 mg/kg per day of the mu opioid L-alpha-acetylmethadol (LAAM). This study examined a role for monoamines in the directly observable and physiologic manifestations of LAAM withdrawal induced by naltrexone in the same monkeys. The effects of saline, clonidine (0.032 mg/kg), haloperidol (0.032 mg/kg), cocaine (1.0 mg/kg), amphetamine (1.0 mg/kg) and imipramine (10.0 mg/kg) were examined in LAAM-dependent monkeys that subsequently received saline or naltrexone (0.0001-1.0 mg/kg). Naltrexone dose-dependently increased respiration, abdominal rigidity and salivation. Clonidine attenuated each of these withdrawal signs, whereas haloperidol increased some (i.e. respiration) and decreased others (i.e. salivation). When administered alone, cocaine and amphetamine increased respiration and also increased the respiratory stimulant effects of naltrexone; cocaine and amphetamine did not attenuate any measure of withdrawal. With the exception of a decrease in naltrexone-induced salivation, imipramine was without effect. These results are strikingly different from results in these same LAAM-dependent monkeys showing that cocaine and amphetamine, but not clonidine, markedly attenuated a naltrexone discriminative stimulus. That monoaminergic ligands differentially alter the directly observable and discriminative stimulus effects of naltrexone in LAAM-dependent monkeys supports the view that monoamines differentially mediate the physical manifestations (norepinephrine) and subjective experience (dopamine) of opioid withdrawal.
Sell
S L
SL
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas, USA.
McMahon
L R
LR
Koek
W
W
France
C P
CP
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000661:Amphetamine / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000502:physiology*; D003000:Clonidine / Q000627:therapeutic use; D003042:Cocaine / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use; D007099:Imipramine / Q000627:therapeutic use; D008253:Macaca mulatta; D008297:Male; D008692:Methadyl Acetate / Q000009:adverse effects*; D009127:Muscle Rigidity / Q000517:prevention & control; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D015656:Respiratory Mechanics / Q000187:drug effects; D012472:Salivation / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology*
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D000929:Antidepressive Agents, Tricyclic; D015306:Biogenic Monoamines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D009271:Naltrexone; D000661:Amphetamine; D003042:Cocaine; D006220:Haloperidol; D008692:Methadyl Acetate; D003000:Clonidine; D007099:Imipramine