Independence of benzodiazepine and opiate action in the suppression of isolation distress in rat pups.
To determine whether benzodiazepines (BDZs) quiet isolation distress in 10-day-old rat pups by causing a release of endogenous opioids, a blockade of the effects of chlordiazepoxide (CDP) by the opiate antagonist naltrexone (NLX) was sought. Nonsedating doses of morphine (MOR) (0.125 mg/kg) and CDP (2.0 mg/kg) were equally effective in reducing ultrasonic vocalizations and other indices of isolation distress. Appropriate blocking agents NLX, (0.5 mg/kg) against MOR and Ro 15-1788 (4.0 mg/kg) against CDP returned distress measures to levels of saline-treated rat pups. However, NLX failed to reverse the quieting effects of CDP. If CDP potentiates endogenous opioid release, then NLX should block the CDP effect. A higher dose of CDP did not reveal a release of endogenous opioids, and a higher dose of NLX did not antagonize CDP. The quieting effects of BDZs on isolation distress do not appear to be mediated by the opiate system.
Carden
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Department of Psychiatry, New York State Psychiatric Institute, New York 10032.
Hofer
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D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012934:Social Isolation; D014828:Vocalization, Animal / Q000187:drug effects*
D005442:Flumazenil; D009271:Naltrexone; D002707:Chlordiazepoxide; D009020:Morphine