The effects of the GABAA antagonist bicuculline on cocaine self-administration in rats exposed to lead during gestation/lactation

• Published in: Pharmacology, biochemistry and behavior Vol. 80; no. 4; pp. 611 - 619
• Main Authors: VALLES, Rodrigo, ROCHA, Angelica, CARDON, Aaron, BRANON, Gerald R, NATION, Jack R
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01.04.2005
• Subjects: Animals; Animals, Newborn - physiology; Bicuculline - pharmacology; Biological and medical sciences; Body Weight - drug effects; Cocaine-Related Disorders - psychology; Conditioning, Operant - drug effects; Dose-Response Relationship, Drug; Drug addictions; Eating - drug effects; Female; GABA Antagonists - pharmacology; GABA-A Receptor Antagonists; Lead - pharmacology; Medical sciences; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Reward; Self Administration; Toxicology; Lactation; Rat; CNS stimulant; Psychotropic; Rodentia; Exposure; Self administration; Breast feeding; Stress; Heavy metal; Gabaergic receptor; Local anesthetic; Pregnancy; Ester; Alkaloid; Vertebrata; Mammalia; Animal; Neurotransmitter; GABA; Lead; Cocaine; Drug of abuse; Antagonist
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2005.01.011

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.