Pharmacotherapy to treat stimulant use disorders continues to be an unmet medical need. Some evidence supports both the role of
opioids in mediating abuse-related
amphetamine effects and the potential utility of
opioid antagonists as therapeutic candidates for treating
amphetamine abuse. This study used intracranial self-stimulation (ICSS) to evaluate effects of exposure to and termination of
naltrexone maintenance on rewarding
amphetamine effects in an ICSS procedure in rats.
Morphine and
cocaine were included as positive and negative controls, respectively. Male Sprague-Dawley rats (N = 40) were trained to lever press for electrical brain stimulation to the medial forebrain bundle via an
implanted electrode. Rats were then implanted with osmotic pumps delivering
naltrexone (0.001 mg/kg/h, SC, 0.01 mg/kg/h, SC, or 0.1 mg/kg/h, SC) or saline for 14 days. Cumulative dose-effect curves were determined for
amphetamine (0.032 mg/kg to 0.32 mg/kg),
cocaine (1 mg/kg to 10 mg/kg), and
morphine (1 mg/kg to 10 mg/kg) during the 2nd week of
naltrexone maintenance. Additionally, dose-effect curves for
morphine and
amphetamine were determined again 24 hr after pump removal. Our results suggest that (a) exposure to and termination of
naltrexone maintenance do not affect baseline ICSS responding, (b)
naltrexone doses sufficient to antagonize
morphine did not alter
amphetamine or
cocaine effects, and (c) termination of
naltrexone treatment produced weak evidence for increased
morphine sensitivity but no change in
amphetamine effects. Our results do not support
naltrexone as a
pharmacotherapy for
amphetamine and
cocaine abuse and also suggest that termination from chronic
naltrexone does not increase sensitivity to abuse-related
morphine or
amphetamine effects in ICSS. (PsycINFO Database Record