Behavioral evidence for dopaminergic supersensitivity after chronic haloperidol.
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Administration, Oral↗
Biomedical subjects
M D Hynes
Publications and source records attributed to M D Hynes.
Effect of apomorphine and nigrostriatal lesions on aggression and striatal dopamine turnover during morphine withdrawal: evidence for dopaminergic supersensitivity in protracted abstinence.
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Aggression↗
Cross-tolerance studies distinguish morphine- and metkephamid-induced analgesia.
In vitro data demonstrate that metkephamid (LY127623), an analog of methionine enkephalin, has a high affinity for the delta opioid receptor, as well as the mu-receptor. Data generated utilizing two in vivo measures of receptor selectivity, furthermore, indicate that metkephamid's analgesic activity is in part mediated by delta opioid receptors. The analgesic activity of metkephamid was investigated in the mouse writhing assay following chronic treatment with morphine, the prototypic mu agonist. Mice were treated chronically with increasing doses of morphine or saline and the inhibition of writhing measured in response to an acute injection of morphine or metkephamid. The dose response curve for morphine was shifted to the right 3- to 4-fold following chronic administration of morphine. In contrast, no such shift in the dose response curve for metkephamid was observed in these morphine-tolerant mice. In a further series of tests, a 50 mg/kg dose of naloxazone 20 hr prior to the assessment of morphine or metkephamid analgesia in the mouse hot plate test substantially shifted the dose-response curve for morphine to the right, while leaving the dose-response curve for metkephamid unchanged. These results suggest that delta-receptor activation contributes to the analgesia produced by metkephamid.
Analgesia↗
Effects of haloperidol, methyltyrosine and morphine on recovery from lesions of lateral hypothalamus.
In rats loss of body weight and lethality were measured after bilateral electrolytic lesions of the lateral hypothalamus. The rats with incomplete lesions initially lost body weight but recovered spontaneously. Treatment with haloperidourgery facilitated the recovery in those rats. The rats with more complete lesions lost body weight which resulted in eventual death. Treatment with haloperidol (4 mg/kg/day) or morphine (60 mg/kg/day) given daily for six days before surgery promoted recovery and reduced the incidence of death. The drugs used in this study inhibit activity of brain dopamine receptors to result in the supersensitivity and/or promotion of regenerative processes. These effects are considered to be related to the facilitation of recovery from nerve injury.
Animals↗