Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jan 1987
Determination of cross tolerance in rat spinal cord using intrathecal infusion via sequential mini-osmotic pumps.
Continuous intrathecal (IT) infusion via ALZET mini-osmotic pumps was used to induced spinal tolerance to morphine in the rat. Naloxone (1 mg/kg IP), injected on day 3 of continuous IT morphine (10 micrograms/hr), produced mild withdrawal symptoms in all morphine-treated animals. In rats pretreated with continuous IT morphine (10 micrograms/hr) or saline, systemic morphine (2, 4, 8, 10 and 15 mg/kg IP) produced equivalent, dose-dependent antinociception using the tail-flick and paw pressure tests. ⋯ A sequential, double mini-osmotic pump technique for cross tolerance studies in rat spinal cord is described. In rats pretreated with continuous IT norepinephrine for 4 days, the antinociceptive actions of continuous IT morphine were reduced but not significantly different from saline-pretreated animals. These data suggest that morphine, injected into the spinal cord, does not produce behavioural analgesia by activation of local adrenergic systems.
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Pharmacol. Biochem. Behav. · Jan 1987
Interactions of clonidine with phencyclidine and ketamine: studies of radial maze performance and righting reflex in rats.
Rats were trained to obtain food pellets in an 8-arm radial maze until a criterion of 89% efficiency, i.e., all arms entered within 9 arm entries, was reached in 5 consecutive sessions. Decreases in efficiency caused by phencyclidine (PCP; 4 to 9 mg/kg, IP, 15 min before testing) or ketamine (25 mg/kg, IP, 5 min) were attenuated when subjects were pretreated with clonidine (0.05 mg/kg, IP, 30 min). However, significant improvements in performance in the maze were not observed when clonidine (0.05 to 0.4 mg/kg, IP) was administered 15 min after PCP (9 mg/kg, IP, 45 min). ⋯ When clonidine (0.05 mg/kg, IP) was administered 15 minutes before [3H]PCP (40 microCi/kg, IP), brain levels of tritium were reduced by 42 to 55%. The present findings do not support the suggestion that clonidine may be useful in the treatment of PCP intoxication. The data does indicate that pretreatment of surgical patients with clonidine may reduce the dose of ketamine required for anesthesia.