5-HT(1A) and 5-HT(2A) serotonin receptor turnover in adult rat offspring prenatally exposed to cocaine.
This study investigated the effects of prenatal exposure to cocaine on the intracellular kinetics (i.e. rate constant of receptor production and degradation) that govern the maintenance and regulation of cortical 5-HT(1A) and 5-HT(2A) receptor densities in offspring. Adult male rat offspring, prenatally exposed to saline or (-) cocaine (15 mg/kg, s.c., b.i.d, from gestational day 13 through 20), were injected with either vehicle or the irreversible receptor antagonist, EEDQ (10 mg/kg, s.c.), and sacrificed at various post-injection times to monitor the recovery of receptor densities in cerebral cortex. In both saline and cocaine exposed offspring, initial EEDQ-induced reductions (>80%) in 5-HT(1A) and 5-HT(2A) receptor densities were followed by a time-dependent repopulation that reached steady state ([B(max)](ss)) densities comparable to non-EEDQ treated controls by day 10 post-treatment. Calculation of 5-HT(1A) receptor kinetic parameters indicated that prenatal exposure to cocaine did not significantly alter: (1) the receptor production rate (saline: 0.809 fmol/mg protein/h; cocaine: 0.724 fmol/mg protein/h), (2) the receptor degradation rate constant (saline: 0.0063 h(-1); cocaine: 0.0062 h(-1)) or (3) the half-life (t(1/2)) of receptor repopulation (saline: 109.2 h; cocaine: 111.5 h). Similarly, 5-HT(2A) receptor rate constants for production (1. 550 fmol/mg protein/h) and degradation (0.0061 h(-1)) and consequently, t(1/2) (113.2 h), were not significantly altered by prenatal exposure to cocaine. These data suggest that within homogenates of cerebral cortex, prenatal exposure to cocaine did not alter the overall intracellular processes that underlie receptor production or degradation and determine steady state densities of 5-HT(1A) or 5-HT(2A) receptors.
Vicentic
A
A
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA.
Cabrera-Vera
T M
TM
Pinto
W
W
Battaglia
G
G
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D020127:Recovery of Function / Q000502:physiology; D013997:Time Factors
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D003042:Cocaine