Local μ and δ opioid receptors regulate amphetamine-induced behavior and neuropeptide mRNA in the striatum

The purpose of this study was to investigate the role that μ and δ opioid receptor blockade has upon stimulant-induced behavior and neuropeptide gene expression in the striatum. Acute administration of amphetamine (2.5 mg/kg i.p.) caused an increase in behavioral activity and preprodynorphin, substance P, and preproenkephalin mRNA expression. Intrastriatal infusion of the μ opioid antagonist, H- d-Phe-Cys-Tyr- d-Trp-Arg-Thr-Pen-Thr-NH 2 (CTAP), or the δ opioid antagonist, H-Tyr-Tic[CH 2NH]-Phe-Phe-OH (TIPPψ), significantly decreased amphetamine-induced vertical activity. However, only CTAP reduced amphetamine-induced distance traveled. Quantitative in situ hybridization histochemistry revealed that CTAP blocked amphetamine-induced preprodynorphin and substance P mRNA. However, preproenkephalin mRNA levels in the dorsal striatum were increased to the same extent by CTAP, amphetamine, or a combination of the two drugs. In contrast, TIPPψ significantly decreased amphetamine-induced mRNA expression of all three neuropeptides. These data indicate that both μ and δ receptor subtypes differentially regulate amphetamine-induced behavior and neuropeptide gene expression in the rat striatum.