Effects of environmental enrichment on sensitivity to mu, kappa, and mixed-action opioids in female rats

Abstract

Several studies report that environmental enrichment enhances sensitivity to opioid receptor agonists in male rats. Very few studies have examined the effects of enrichment in female rats, and thus it is not clear whether females are similarly sensitive to these effects. Consequently, the purpose of the present study was to examine the effects of environmental enrichment on sensitivity to representative mu, kappa, and mixed-action opioids in female rats. Following a protocol established in males, females were obtained at weaning and randomly assigned to two groups immediately upon arrival: isolated rats were housed individually with no visual or tactile contact with other rats; enriched rats were housed in groups of four in large cages and given various novel objects on a regular basis. After 6 weeks under these conditions, the antinociceptive effects of mu (morphine, levorphanol), kappa (spiradoline, U69,593), and mixed-action (buprenorphine, butorphanol) opioids were examined in a warm-water, tail-withdrawal procedure. All the opioids examined produced dose-dependent increases in antinociception; however, no differences in opioid sensitivity were observed between the two groups. To determine whether these findings were consistent across behavioral endpoints, the antidiuretic effects of representative mu opioids, and the diuretic effects of representative kappa opioids, were examined in female rats reared under isolated or enriched conditions for 10 weeks. Similar to that seen in the antinociceptive experiment, no significant differences in opioid sensitivity were observed between groups. These data indicate that environmental enrichment does not alter sensitivity to the effects of opioid receptor agonists in female rats, and suggest that females may respond differently to environmental enrichment than males. Keywordsantidiuresis; antinociception; diuresis; enrichment; female; isolation; opioid; rat A large number of studies reveal that environmental manipulations during critical periods in development can influence the physical maturation of the nervous system and produce functional effects on behavior. For example, male rats reared under conditions of environmental enrichment (i.e., conditions in which rats were housed together in large groups and provided with novel objects on a regular basis) had greater cortical mass [1,2], had greater dendritic branching on cortical neurons [3,4], and performed better in learning and memory tasks [5,6] than animals reared in isolation under impoverished conditions. Interestingly, these same types of manipulations can also influence an organism's sensitivity to the neurochemical Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be ...

Sex differences in kappa opioid pharmacology

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Reduction of the sevoflurane minimum alveolar concentration induced by methadone, tramadol, butorphanol and morphine in rats

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Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

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