Evidence for the behavioral supersensitivity of dopamine D2 receptors without receptor up-regulation in morphine-abstinent rats.
The effect of morphine tolerance-dependence and abstinence on the characteristics of dopamine D2 receptors in brain regions and spinal cord was determined in the rat. Male Sprague-Dawley rats were implanted s.c. under light ether anesthesia with 6 morphine pellets for a 7-day period, each containing 75 mg of morphine free base. Rats implanted with placebo pellets served as controls. This procedure resulted in the development of tolerance to morphine as evidenced by decreased analgesic response to a challenge dose of morphine. Similarly, the development of physical dependence was evidenced by a decrease in body weight and colonic temperature after morphine pellet removal (withdrawal). The binding characteristics (Bmax and Kd values) of [3H]spiroperidol to dopamine D2 receptors were determined in the tissues of morphine-tolerant and morphine-abstinent rats. In the tolerant rats, the pellets were left intact at the time of sacrificing, whereas, in the abstinent rats the pellets were removed 18 h prior to sacrificing. The binding of [3H]spiroperidol was determined in membranes prepared from brain regions (hypothalamus, hippocampus, cortex, pons and medulla, midbrain, corpus striatum and amygdala) and spinal cord of rats from various treatment groups. [3H]Spiroperidol bound to brain regions and spinal cord at a single high affinity site. The Bmax or the Kd values in brain regions and spinal cord of morphine-tolerant and -abstinent rats did not differ from their respective placebo controls. The behavioral responses to a selective dopamine D2 receptor agonist, 2-bromo-alpha-ergocryptine were also determine in the morphine-abstinent rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Reddy
P L
PL
Department of Pharmacodynamics, University of Illinois, Chicago 60612.
Veeranna
Thorat
S N
SN
Bhargava
H N
HN
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D004361:Drug Tolerance; D007700:Kinetics; D008297:Male; D009021:Morphine Dependence / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D015854:Up-Regulation / Q000187:drug effects*
D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D013134:Spiperone