The effects of diazepam dependence and withdrawal on morphine-induced antinociception and changes in locomotion in male and female rats

Male and female rats were exposed for 3 weeks to diazepam (DZ)-filled or empty capsules (CTR) prior to the daily administration of morphine (MOR, 5 mg/kg, IP) for 5 days. Thereafter, capsules were removed and 48 h later MOR was injected for the next 5 days. The tail-flick latency (TFL) was measured...

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Bibliographic Details
Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2001-07, Vol.69 (3), p.475-484
Main Authors: Wala, Elzbieta P., Sloan, Jewell W., Jing, Xin, Holtman, Joseph R.
Format: Article
Language:English
Subjects:
Analgesics
Analgesics - pharmacology
Analgesics, Opioid - pharmacology
Animals
Anti-Anxiety Agents - pharmacology
antinociception
Biological and medical sciences
Diazepam - pharmacology
Diazepam dependence
Female
Gender
Locomotion
Locomotion - drug effects
Locomotion - physiology
Male
Medical sciences
Morphine - pharmacology
Morphine analgesia
Morphine tolerance
Neuropharmacology
Pain Measurement - drug effects
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Sex Factors
Substance Withdrawal Syndrome
Substance-Related Disorders
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Summary:Male and female rats were exposed for 3 weeks to diazepam (DZ)-filled or empty capsules (CTR) prior to the daily administration of morphine (MOR, 5 mg/kg, IP) for 5 days. Thereafter, capsules were removed and 48 h later MOR was injected for the next 5 days. The tail-flick latency (TFL) was measured prior to and 15, 30, and 60 min after MOR assessed analgesia. Locomotion (LOC) was determined before and 15 min after injection. Prior to MOR injection (baseline), male rats were more sensitive to the thermal stimulus and were less active than female rats. Daily MOR injections neither affected the baseline TFL nor LOC. Regardless of gender, MOR produced greater analgesia in DZ-dependent and withdrawn rats than in CTR. MOR analgesia was greater in DZ-dependent male than in female rats. Gender differences in MOR analgesia were not of statistical significance in DZ-withdrawn rats. The first dose of MOR produced more depression of LOC in DZ-dependent female than in male rats. Across the time of MOR injections, female DZ-dependent and withdrawn rats were less active than CTR. LOC increased with repeated administration of MOR in all groups of rats. In summary, DZ dependence and withdrawal enhanced MOR analgesia in rats of both sexes. Regardless of chronic treatment, MOR produced more analgesia and less depression of LOC in male than in female rats. It is suggested that a decrease in the function of the GABAergic system plays a role in alteration of MOR analgesia.
ISSN:0091-3057
1873-5177
DOI:10.1016/S0091-3057(01)00570-6