Modulation of brain alpha 2-adrenoceptor and mu-opioid receptor densities during morphine dependence and spontaneous withdrawal in rats.

Abstract

The densities of brain alpha 2-adrenoceptors and mu-opioid receptors, quantitated by means of the binding of the agonists [3H]clonidine and [3H]dihydromorphine, respectively, were studied during the development of morphine dependence and spontaneous withdrawal in the rat. The oral administration of morphine (12-130 mg/kg for 3-21 days) led to inconsistent changes in alpha 2-adrenoceptor density while the density of mu-opioid receptors was down-regulated. In contrast, spontaneous opiate withdrawal (3-72 h) significantly increased the density of alpha 2-adrenoceptors while the density of mu-opioid receptors was rapidly up-regulated to control values. In the hypothalamus, but not in other brain regions, the increase in alpha 2-adrenoceptor density after withdrawal followed a time course (3-72 h) related to the severity of the abstinence syndrome. Thus, there was a positive and significant correlation between the severity of withdrawal and the density of alpha 2-adrenoceptors in the hypothalamus. Short-term treatment with clonidine (2 x 0.5 mg/kg, i.p.) prevented the morphine withdrawal-induced increases in alpha 2-adrenoceptor density in various brain regions, but not in the hypothalamus. The main results suggest that modulation of hypothalamic alpha 2-adrenoceptor density during morphine withdrawal is a relevant physiological mechanism by which the opiate abstinence syndrome is counteracted.

• Authors: I Ulibarri, J A García-Sevilla, L Ugedo
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 336 Issue 5 Pg. 530-7 (Nov 1987) ISSN: 0028-1298 [Print] Germany
• PMID: 2830545 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Adrenergic, alpha
• Receptors, Opioid
• Morphine
• Dihydromorphine
• Clonidine

Topics

• Animals
• Brain (metabolism)
• Brain Stem (metabolism)
• Cerebral Cortex (metabolism)
• Clonidine (metabolism)
• Corpus Striatum (metabolism)
• Dihydromorphine (metabolism)
• Hypothalamus (metabolism)
• Male
• Morphine (adverse effects)
• Morphine Dependence (metabolism)
• Rats
• Rats, Inbred Strains
• Receptors, Adrenergic, alpha (drug effects, metabolism)
• Receptors, Opioid (drug effects, metabolism)
• Substance Withdrawal Syndrome (metabolism)