The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · May 1988
Intrathecal morphine and clonidine: antinociceptive tolerance and cross-tolerance and effects on blood pressure.
The effects of acute and chronic intrathecal (i.t.) administration of the opioid receptor agonist, morphine, or the alpha-2 adrenoceptor agonist, clonidine, on nociception and blood pressure were examined in rats. In rats lightly anesthetized with pentobarbital, morphine produced dose-dependent inhibition of the nociceptive tail-flick reflex (ED50 = 10.0 micrograms) and small, non-dose-related pressor effects. These effects were antagonized by pretreatment with the opioid receptor antagonist naloxone (30.0 micrograms i.t.), whereas the alpha-2 adrenoceptor antagonist yohimbine (30.0 micrograms i.t.) potentiated the pressor effects and did not alter the antinociceptive effects of morphine. ⋯ These results indicate that the antinociceptive effects of acute i.t. morphine and clonidine are mediated by spinal opioid and alpha-2 adrenergic receptors, respectively. However, tolerance to and cross-tolerance between i.t. morphine and i.t. clonidine suggest that spinal opioid and alpha-2 adrenergic systems interact in producing antinociception. These systems also appear to interact in complex ways to exert effects on blood pressure.