Aversive properties of naloxone in non-dependent (naive) rats may involve blockade of central beta-endorphin.
The present study examines the influence of destruction of the medio-basal arcuate hypothalamus (MBH), the primary site of synthesis of central pools of beta-endorphin (beta-EP), upon the aversive properties of naloxone in a conditioned place preference paradigm. Bilateral radiofrequency lesions of the MBH resulted in a pronounced fall in levels of immunoreactive beta-EP in the brain. Lesioned rats, in contrast to non-operated animals, showed a clear reduction in the conditioned place aversion produced by naloxone. However, they showed no loss of the conditioned preference produced by the mu-selective opioid receptor agonist, morphine, or the conditioned aversion produced by the kappa-selective agonist, U50-488. In contrast to the effect of the lesions, suppression of circulating beta-EP by dexamethasone treatment failed to influence conditioning produced by naloxone. Thus, the data indicate that the aversive properties of naloxone are attenuated by disruption of central (but not peripheral) beta-EP activity. We suggest that these properties of naloxone reflect an antagonism of beta-EP activity in the brain. In addition, the data indicate that differing mechanisms underlie the aversive actions of naloxone as compared to U50-488.
Mucha
R F
RF
Millan
M J
MJ
Herz
A
A
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002755:Choice Behavior / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D004399:Dynorphins / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D017473:Receptors, Opioid, kappa; D013037:Spatial Behavior; D001615:beta-Endorphin
D004723:Endorphins; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D001615:beta-Endorphin; D004399:Dynorphins; D003907:Dexamethasone