Changes in alpha 2-adrenoceptor number and function in brains of morphine-dependent rats

Autor: C B, Smith, H C, Moises, R N, Spengler, P J, Hollingsworth
Rok vydání: 1989
Předmět:
Zdroj: European journal of pharmacology. 161(2-3)
ISSN: 0014-2999
Popis: 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.
Databáze: OpenAIRE