Biomaterial Database

Prenatal exposure to cocaine increases the rewarding potency of cocaine and selective dopaminergic agonists in adult mice. 2008

C J Malanga, and Thorfinn T Riday, and William A Carlezon, and Barry E Kosofsky

Laboratory of Molecular and Developmental Neuroscience, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. malangacj@neurology.unc.edu

BACKGROUND Substance abuse during pregnancy results in persistent affective and behavioral deficits in drug-exposed children, and increased rates of substance abuse have been observed in young adults prenatally exposed to drugs of abuse. Animal models of prenatal cocaine exposure have yielded differing results depending on the behavioral method used to assess drug potency. METHODS The effects of cocaine, the dopamine D1 agonists SKF-81297 and SKF-82958, and the D2 agonist quinpirole on intracranial self-stimulation were measured in adult Swiss-Webster mice exposed to cocaine in utero (40 mg/kg/day) and vehicle controls with the curve-shift method of brain stimulation-reward (BSR) threshold determination. RESULTS The reward-potentiating effects of cocaine (0.3-30 mg/kg IP) and SKF-82958 but not SKF-81297 on BSR were increased in adult male but not female mice after prenatal cocaine exposure. Quinpirole exerted biphasic effects on BSR, both elevating (0.1-0.3 mg/kg IP) and lowering (1.0-10 mg/kg IP) reward thresholds. Both effects of quinpirole were also enhanced in adult male mice after prenatal cocaine exposure. CONCLUSIONS Prenatal cocaine exposure results in increased reward-potentiating potency of cocaine on BSR in adult mice in a sexually-dimorphic manner. This augmented rewarding effect of cocaine is also associated with increased sensitivity to both D1- and D2-selective agonists.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011297	Prenatal Exposure Delayed Effects	The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH.	Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D003042	Cocaine	An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.	Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D003216	Conditioning, Operant	Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced.	Instrumental Learning,Learning, Instrumental,Operant Conditioning,Conditionings, Operant,Instrumental Learnings,Learnings, Instrumental,Operant Conditionings
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004558	Electric Stimulation	Use of electric potential or currents to elicit biological responses.	Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical