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Developmental disruption of gamma-aminobutyric acid function in the medial prefrontal cortex by noncontingent cocaine exposure during early adolescence.


ABSTRACT: Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further understand the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts medial prefrontal cortex (mPFC) network function in adulthood.A noncontingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days [PD] 35-40) on the overall inhibitory regulation of mPFC activity in adulthood (PD 65-75) by means of histochemical and in vivo electrophysiological measures combined with pharmacologic manipulations.Cocaine exposure during early adolescence yields a distinctive hypermetabolic prefrontal cortex state that was not observed in adult-treated rats (PD 75-80). Local field potential recordings revealed that early adolescent cocaine exposure is associated with an attenuation of mPFC gamma-aminobutyric acid (GABA)ergic inhibition evoked by ventral hippocampal stimulation at beta and gamma frequencies that endures throughout adulthood. Such cocaine-induced mPFC disinhibition was not observed in adult-exposed animals. Furthermore, the normal developmental upregulation of parvalbumin immunoreactivity observed in the mPFC from PD 35 to PD 65 is lacking following early adolescent cocaine treatment.Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders.

SUBMITTER: Cass DK 

PROVIDER: S-EPMC3722277 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Developmental disruption of gamma-aminobutyric acid function in the medial prefrontal cortex by noncontingent cocaine exposure during early adolescence.

Cass Daryn K DK   Thomases Daniel R DR   Caballero Adriana A   Tseng Kuei Y KY  

Biological psychiatry 20130401 7


<h4>Background</h4>Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further understand the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts medial prefrontal cortex (mPFC) network function in adulthood.<h4>Methods</h4>A noncontingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days [PD] 35-40) on the  ...[more]

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