Gestational exposure to nicotine and monoamine oxidase inhibitors influences cocaine-induced locomotion in adolescent rats.
BACKGROUND
Many pregnant women continue to smoke, despite a strong association between maternal smoking and neurobehavioral deficits in the offspring. Although gestational nicotine (GN) treatment in rodents is used as the primary animal model of maternal smoking, tobacco smoke contains more than 4,000 constituents, including monoamine oxidase inhibitors (MAOIs).


OBJECTIVE
The aim of this study was to determine whether there are interactions between the effects of gestational exposure to nicotine and MAOIs on cocaine-induced locomotor sensitization in adolescent rats.


METHODS
Pregnant rats were implanted on day 4 of gestation with osmotic minipumps delivering saline, nicotine (3 mg/kg per day), the MAOIs clorgyline and deprenyl (1 and 0.25 mg/kg per day, respectively), or nicotine/clorgyline/deprenyl (GMN). Adolescent female offspring were tested for cocaine-induced locomotor sensitization. Animals were treated with saline or cocaine (5 or 15 mg/kg, intraperitoneally) daily from postnatal (P) days 32-36 and challenged with cocaine (15 mg/kg) on P51 (day 20).


RESULTS
Group differences were observed in chronic but not acute effects of cocaine. Whereas gestational MAOI treatment, with or without nicotine, increased ambulatory response to cocaine on day 5, the opposite was found for vertical activity. Different adaptive responses were observed on cocaine challenge day. GNM animals exhibited enhanced locomotor activity in the cocaine-associated environment before cocaine challenge on day 20. In contrast, only GN animals exhibited significant locomotor sensitization to the cocaine challenge.


CONCLUSIONS
Gestational nicotine and MAOIs both influence brain development. Such interactions may sensitize adolescents to drug abuse and should be considered in animal models of maternal smoking.
Franke
Ryan M
RM
Department of Pharmacology, School of Medicine, University of California, Irvine CA, 92697, USA.
Belluzzi
James D
JD
Leslie
Frances M
FM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D003010:Clorgyline / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005163:Factor Analysis, Statistical; D005260:Female; D015918:Infusion Pumps, Implantable; D007274:Injections, Intraperitoneal; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology; D012684:Sensory Thresholds / Q000187:drug effects; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D018722:Nicotinic Agonists; D014662:Vasoconstrictor Agents; D012642:Selegiline; D009538:Nicotine; D003042:Cocaine; D003010:Clorgyline