Phenylpropanolamine Hydrochloride

Globally, phenylpropanolamine (PPA) is a prevalent primary active ingredient in over-the-counter cough and cold, as well as weight-loss medications. Previously, we showed that a sensitization of cocaine-induced glutamate release within the nucleus accumbens (NAC) and the expression of cocaine-conditioned reward is not apparent in adult mice with a prior history of repeated PPA exposure during adolescence. As NAC glutamate is a purported driver of cocaine reward and reinforcement, the present study employed in vivo microdialysis and immunoblotting approaches to inform as to the receptor and transporter anomalies that might underpin the disrupted glutamate response to cocaine in adolescent PPA-exposed mice. For this, male and female C57BL/6J mice were pretreated, once daily, with either 0 or 40mg/kg PPA during post-natal days 35-44. Adolescent PPA pretreatment significantly altered the expression of mGlu2/3 and α2 receptors in the NAC, with less robust changes detected for EAAT2, D2 receptors, DAT and NET. However, we detected no overt change in the capacity of these receptors or transporters to affect extracellular glutamate levels in adolescent PPA-pretreated mice. The present findings contrast with the pronounced changes in the capacity of mGlu2/3 receptors, EAAT, DAT and NET to regulate NAC extracellular glutamate reported previously for juvenile PPA-pretreated mice, indicating further that the long-term biochemical consequences of PPA depend on the critical period of neurodevelopment during which an individual is PPA-exposed, although the specific biomolecular changes underpinning the cocaine phenotype produced by adolescent PPA remain to be elucidated.