Social and environmental influences on opioid sensitivity in rats: importance of an opioid's relative efficacy at the mu-receptor.
BACKGROUND
Evidence indicates that social and environmental enrichment can influence the functional maturation of the central nervous system and may affect an organism's sensitivity to centrally acting drugs.


OBJECTIVE
The purpose of the present study was to examine the effects of social and environmental enrichment on sensitivity to mu-opioids possessing a range of relative efficacies at the mu-receptor.


METHODS
Rats were obtained at weaning (21 days) and divided into two groups immediately upon arrival. Isolated rats were housed individually in opaque laboratory cages with no visual or tactile contact with other rats; enriched rats were housed socially in groups of four in large cages and given various novel objects on a daily basis. After 6 weeks under these conditions, the effects of morphine, levorphanol, buprenorphine, butorphanol, and nalbuphine were examined in the warm-water, tail-withdrawal procedure and the place-conditioning procedure.


RESULTS
In the tail-withdrawal procedure, isolated and enriched rats did not differ in sensitivity to morphine (1.0-30 mg/kg) and levorphanol (0.3-10 mg/kg), but enriched rats were more sensitive to buprenorphine (0.03-3.0 mg/kg), butorphanol (0.3-30 mg/kg), and nalbuphine (0.3-30 mg/kg). In drug combination tests, butorphanol and nalbuphine antagonized the effects of morphine in isolated rats under conditions in which they produced high levels of antinociception in enriched rats. In the place-conditioning procedure, doses of 10 morphine and 3.0 levorphanol established a place preference in both groups of rats, whereas doses of 0.3 buprenorphine, 3.0 butorphanol, and 10 nalbuphine established a place preference only in enriched rats.


CONCLUSIONS
These findings may be taken as evidence that enriched rats are more sensitive than isolated rats to the effects of lower-efficacy mu-opioids and that social and environmental enrichment leads to functional alterations in opioid receptor populations.
Smith
Mark A
MA
Department of Psychology, Davidson College, Davidson, NC 28035-7037, USA. masmith@davidson.edu
Chisholm
Kara A
KA
Bryant
Paul A
PA
Greene
Jennifer L
JL
McClean
Jacob M
JM
Stoops
William W
WW
Yancey
David L
DL
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology; D002077:Butorphanol / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007981:Levorphanol / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009266:Nalbuphine / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology*; D012931:Social Environment; D012934:Social Isolation / Q000523:psychology*; D014886:Weaning
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D007981:Levorphanol; D002047:Buprenorphine; D009020:Morphine; D009266:Nalbuphine; D002077:Butorphanol