Presynaptic alpha 2 adrenoreceptor function in dependent rats before and after morphine withdrawal.
Changes in the number of alpha 2 adrenoreceptors in the hippocampus, as measured by the specific binding of 3H-clonidine, were compared to changes in presynaptic alpha 2 adrenoreceptor function in electrically stimulated hippocampal slices. In dependent rats the specific binding of 3H-clonidine was reduced significantly. At 32 h after withdrawal binding began to return toward normal values, and at 72 h after withdrawal was significantly greater than that seen in saline-treated rats. In hippocampal slice experiments sensitivity to clonidine was significantly decreased in morphine-dependent animals and returned toward normal values after withdrawal. At 72 h after withdrawal, the sensitivity to clonidine of the presynaptic alpha 2 adrenoreceptor remained depressed although receptor density as measured in the binding studies was increased. This study suggests that the changes in the function of presynaptic alpha 2 adrenoreceptors might be important in the development of dependence upon morphine.
Moises
H C
HC
Department of Physiology, University of Michigan, Ann Arbor 48109.
Smith
C B
CB
Spengler
R N
RN
Hollingsworth
P J
PJ
D000818:Animals; D003000:Clonidine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000503:physiopathology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D011943:Receptors, Adrenergic, beta; D009020:Morphine; D003000:Clonidine; D009638:Norepinephrine