Aversive Properties of Naloxone in Non-dependent (naive) Rats May Involve Blockade of Central Beta-endorphin
Overview
Authors
Affiliations
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.
Galiza Soares J, Sutley-Koury S, Pomrenze M, Tucciarone J Front Neuroanat. 2025; 18:1521016.
PMID: 39917739 PMC: 11798945. DOI: 10.3389/fnana.2024.1521016.
Toorie A, Hall C, Vassoler F, Peltz G, Byrnes E Psychopharmacology (Berl). 2024; 241(7):1435-1446.
PMID: 38503843 DOI: 10.1007/s00213-024-06574-0.
Le A, Funk D, Coen K, Tamadon S, Shaham Y Neuropsychopharmacology. 2017; 43(4):838-850.
PMID: 28589966 PMC: 5809779. DOI: 10.1038/npp.2017.120.
Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward.
Al-Hasani R, McCall J, Shin G, Gomez A, Schmitz G, Bernardi J Neuron. 2015; 87(5):1063-77.
PMID: 26335648 PMC: 4625385. DOI: 10.1016/j.neuron.2015.08.019.
Behavioral architecture of opioid reward and aversion in C57BL/6 substrains.
Kirkpatrick S, Bryant C Front Behav Neurosci. 2015; 8:450.
PMID: 25628547 PMC: 4290583. DOI: 10.3389/fnbeh.2014.00450.