Protracted 'anti-addictive' effects of adolescent phenylpropanolamine exposure in C57BL/6J mice

Exposure to the once highly prevalent over-the-counter (OTC) sympathomimetic phenylpropanolamine (PPA; +/--norephedrine) during pre-adolescence alters the developmental trajectory of catecholamine and amino acid neurotransmitter systems in the nucleus accumbens (NAC) that culminate in a 'pro-ad...

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Bibliographic Details
Published in:Addiction biology 2008-09, Vol.13 (3-4), p.310-325
Main Authors: Penzner, Jeffery H, Thompson, Daria L, Arth, Cory, Fowler, Jaclyn K, Ary, Alexis W, Szumlinski, Karen K
Format: Article
Language:English
Subjects:
Age Factors
Amino Acids - metabolism
Animals
Behavior, Addictive
Catecholamines - metabolism
Cocaine - administration & dosage
Cocaine - pharmacology
Conditioning (Psychology)
Dose-Response Relationship, Drug
Female
Glutamic Acid - metabolism
Locomotion - drug effects
Male
Mice
Mice, Inbred C57BL
Narcotics - administration & dosage
Narcotics - pharmacology
Neurotransmitter Agents - metabolism
Nucleus Accumbens - drug effects
Phenotype
Phenylpropanolamine - administration & dosage
Phenylpropanolamine - pharmacology
Sympathomimetics - administration & dosage
Sympathomimetics - pharmacology
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Summary:Exposure to the once highly prevalent over-the-counter (OTC) sympathomimetic phenylpropanolamine (PPA; +/--norephedrine) during pre-adolescence alters the developmental trajectory of catecholamine and amino acid neurotransmitter systems in the nucleus accumbens (NAC) that culminate in a 'pro-addictive' phenotype in adulthood. Thus, the present study sought to extend these earlier data by examining the long-term consequences of repeated PPA treatment during adolescence upon the behavioral and neurochemical responses to cocaine. For this, C57BL/6J mice were pre-treated with PPA (0-40 mg/kg) during postnatal days 35-44, and the capacity of cocaine (4 x 15 mg/kg) to elicit a conditioned place-preference, as well as behavioral and neurochemical sensitization within the NAC, were then assessed in adulthood. While adolescent PPA exposure did not influence spontaneous locomotor activity or the motor responses to either acute or repeated cocaine (4 x 15 mg/kg), PPA pre-exposure dose-dependently reduced the expression of a conditioned place-preference. As observed previously for juvenile PPA treatment, adolescent PPA administration blunted the dopamine and norepinephrine response to acute cocaine, prevented the development of catecholamine sensitization but did not influence cocaine-induced elevations in serotonin. However, unlike juvenile PPA treatment, adolescent PPA also prevented the development of glutamate sensitization within the NAC. These data provide evidence that adolescent exposure to a formerly prevalent OTC sympathomimetic produces protracted effects upon cocaine-induced changes in NAC glutamate transmission that may reduce vulnerability to cocaine addiction in later life and further the hypothesis that early exposure to sympathomimetic drugs may be an environmental factor contributing to the etiology of addiction.
ISSN:1355-6215
1369-1600
DOI:10.1111/j.1369-1600.2008.00101.x