The effects of the GABAA antagonist bicuculline on cocaine self-administration in rats exposed to lead during gestation/lactation.
The present investigation examined the effects of perinatal lead exposure on cocaine self-administration following a GABAA antagonist pretreatment. Female rats were exposed to either 0 or 16 mg lead daily for 30 days prior to breeding with unexposed males. Beginning on postnatal day (PND) 75, control (N=10) and lead-exposed (N=8) animals were trained to self-administer 0.50 mg/kg cocaine intravenously (IV). After stable responding was established, animals were tested at 0.03 and 0.06 mg/kg cocaine delivered intravenously (IV), combined with intraperitoneal (IP) administration of either saline, 0.50, 1.00 or 2.00 mg/kg bicuculline (a GABAA antagonist). The results showed that control animals increased self-administration responding at a cocaine dose of 0.06 mg/kg as bicuculline dose increased. Lead-exposed animals exhibited an opposite pattern, i.e., a decrease in active (cocaine) lever responding occurred as the bicuculline dose was increased. Results at the 0.03 mg/kg cocaine dose failed to show group separation, or significant changes consequent to the bicuculline pretreatment. The data suggest that GABA antagonism results in increased reward potency of a low dose of cocaine and further, that this effect is differentially expressed in animals exposed to perinatal lead.
Valles
Rodrigo
R
Department of Psychology, Texas A&M University, College Station, TX 77843, USA.
Rocha
Angelica
A
Cardon
Aaron
A
Bratton
Gerald R
GR
Nation
Jack R
JR
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D007854:Lead / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012646:Self Administration
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D007854:Lead; D001640:Bicuculline