Protracted 'pro-addictive' phenotype produced in mice by pre-adolescent phenylpropanolamine.
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.
Szumlinski
Karen K
KK
Department of Psychology and the Neuroscience Research Institute, University of California at Santa Barbara, Santa Barbara, CA 93106-9660, USA. szumlinski@psych.ucsb.edu
Liu
Andrew
A
Penzner
Jeffery H
JH
Lominac
Kevin D
KD
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D010665:Phenylpropanolamine / Q000097:blood / Q000494:pharmacology*; D012737:Sex Factors; D013239:Stereotyped Behavior / Q000187:drug effects; D013566:Sympathomimetics / Q000097:blood / Q000494:pharmacology*
D000596:Amino Acids; D015306:Biogenic Monoamines; D018765:Dopamine Uptake Inhibitors; D013566:Sympathomimetics; D010665:Phenylpropanolamine; D003042:Cocaine