Abstract
Previous studies have shown that stressors modify endogenous opioid systems. However, the consequences of social stress on the function of endogenous opioid systems is not well documented. The present studies investigated the effect of rank and housing condition on response to SNC-80, a δ receptor agonist. Triad-housed rats were assessed for dominance status by their behavior and alteration in body weights. At 3 and 50 days, triad- and individually housed rats were injected with SNC-80 (35 mg/kg i.p.) or saline, and evaluated using a test battery consisting of open field behaviors, rectal temperature, analgesia, and air-puff-induced ultrasonic vocalizations. After 50 days of housing, plasma corticosterone, adrenal catecholamines, and the density of cyclic[d-penicillamine2-d-penicillamine2]enkephalin-stimulated guanylyl 5′-[γ[35S]thio]-triphosphate binding in the prefrontal cortex, the amygdala, nucleus accumbens, thalamus, arcuate, and median eminence were also determined. The first 24 h of triad housing resulted in loss of body weight in subdominant (βs and γs) but not dominant α rats. SCN-80-induced hypothermia was smaller, and there was no depression of headpoke and locomotor behavior in the periphery and the center of the field of α rats, in contrast to subdominant and singly housed rats. Rank status did not influence SNC-80’s analgesic effect or its inhibition of air-puff-induced ultrasonic vocalizations. Plasma corticosterone levels of αs and γs were lower compared with βs and singly housed rats. Agonist stimulation of δ receptor guanylyl 5′-[γ[35S]thio]-triphosphate binding was lateralized in prefrontal cortex and amygdala, but not nucleus accumbens. Binding was highest in all brain areas of singly housed rats and lowest in the thalamus of β and of γ rats. Lateralized binding in amygdala, high locomotor activity, and sensory sensitivity correlated positively with greater sensitivity to SNC-80-induced depression in these measures. Higher binding in the right amygdala correlated with higher plasma corticosterone levels. These findings indicate that dominant rats displayed stimulant rather than depressant responses to δ-opioid activation. Therefore in rodents rank-related stress can alter responsiveness of the endogenous opioid system, and dominance can increase the excitatory effects of δ agonists.
Footnotes
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Send reprint requests to: Larissa A. Pohorecky, Ph.D., Neuropharmacology Laboratory, Center of Alcohol Studies, Rutgers University, 607 Allison Rd., Piscataway, NJ 08854-8001. E-mail:Larissa{at}RCI.Rutgers.edu
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↵1 This research was supported in part by funds from Sigma Xi, the Rutgers University Honors Program, and National Institutes of Health Grant AA10124. Presented in part at the 27th and 28th Annual Meetings of the Neuroscience Society, 1997 and 1998, respectively.
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↵2 Current address: Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
- Abbreviations:
- DPDPE
- cyclic[d-penicillamine2-d-penicillamine2]enkephalin
- HPA
- hypothalamo-pituitary-adrenal axis
- GTPγS
- guanylyl 5′-[γ-thio]-triphosphate
- PFCx
- prefrontal cortex
- SNC-80
- [(+)-4-[(a-R)-a-((2S,5r)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl-N,N-diethylbenzamide]
- USVs
- ultrasonic vocalizations
- Received June 17, 1998.
- Accepted March 25, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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