Changes in alpha 2-adrenoceptor number and function in brains of morphine-dependent rats.
The effects of long-term treatment of rats with morphine sulfate were assessed upon the specific binding of [3H]clonidine to alpha 2-adrenoceptors on neural membranes isolated from various brain areas and upon the function of presynaptic alpha 2-adrenoceptors during field stimulation of hippocampal slices. Rats were injected with morphine every 8 h for 14 days with doses which started at 10 mg/kg per injection i.p., and which increased every 3 days to a final dose of 100 mg/kg per injection on the last 2 days. At 8 and 32 h after the last injection the Bmax for [3H]clonidine binding to neural membranes from various brain areas was significantly decreased. At the same times, the fractional release of [3H]noradrenaline during field stimulation of hippocampal slices was increased and the sensitivity of the hippocampal slice to clonidine was reduced which indicated the development of a functional subsensitivity of the presynaptic alpha 2-adrenoceptor. These changes in receptor function persisted at 72 h after the last morphine injection although at this time there were marked increases over control values in [3H]clonidine binding to membranes from all rat brain areas except the caudate nucleus. These findings suggest that changes in alpha 2-adrenoceptor number and function which develop during long-term morphine administration might play an important role in opiate dependence.
Smith
C B
CB
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Moises
H C
HC
Spengler
R N
RN
Hollingsworth
P J
PJ
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009021:Morphine Dependence / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D003000:Clonidine