Protracted 'pro-addictive' phenotype produced in mice by pre-adolescent phenylpropanolamine - PubMed (original) (raw)

. 2007 Aug;32(8):1760-73.

doi: 10.1038/sj.npp.1301306. Epub 2007 Jan 24.

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Protracted 'pro-addictive' phenotype produced in mice by pre-adolescent phenylpropanolamine

Karen K Szumlinski et al. Neuropsychopharmacology. 2007 Aug.

Abstract

For decades, the sympathomimetic phenylpropanolamine (PPA; +/- -norepinephrine) was an active ingredient found in popular children's over-the-counter (OTC) cold, cough, and allergy medications. To examine the possibility that pre-adolescent PPA exposure may induce neuroadaptations that influence behavioral and neurochemical responding to cocaine, C57BL/6J mice were pretreated with PPA (0-40 mg/kg) during postnatal days 21-31. The behavioral and neurochemical responses to acute and repeated cocaine (4 x 15 mg/kg) were then assessed in adulthood when the mice were 10 weeks of age. Whereas pre-adolescent PPA exposure did not influence the acute locomotor response to 15 mg/kg cocaine, PPA pre-exposure dose-dependently enhanced the expression of cocaine-induced place conditioning, reduced the expression of locomotor sensitization, but did not influence cocaine-induced stereotypy. Pre-adolescent PPA exposure completely prevented the capacity of cocaine to elevate extracellular levels of catecholamines in the nucleus accumbens, but facilitated the development of cocaine-induced glutamate sensitization. Neither acute nor repeated cocaine altered extracellular GABA levels in the accumbens of control mice; however, 15 mg/kg cocaine lowered GABA levels by approximately 40% in PPA pretreated mice and this effect showed tolerance with repeated cocaine administration. These data provide the first evidence that early exposure to an OTC compound produces protracted effects upon cocaine-induced changes in nucleus accumbens neurotransmission that may contribute to a 'pro-addictive' phenotype in adulthood.

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