Methamphetamine self-administration acutely decreases monoaminergic transporter function

Abstract

Numerous preclinical studies have demonstrated that noncontingent methamphetamine (METH) administration rapidly decreases both dopamine (DA) transporter (DAT) and vesicular monoamine-2 transporter (VMAT-2) function. Because of the importance of transporter function to the abuse and neurotoxic liabilities of METH, and previous research indicating that the effects of noncontingent METH treatment do not necessarily predict effects of contingent exposure, the present study examined the acute impact of METH self-administration on these transporters. Results revealed that five days of METH self-administration (4 h/session; 0.06 mg/infusion) decreased DAT and VMAT-2 activity, as assessed in synaptosomes and vesicles, respectively, prepared from striatal tissue 1 h after the final self-administration session. METH self-administration increased core body temperatures as well. Brain METH and amphetamine (AMPH) levels, assessed 1 h after the final self-administration session, were approximately twice greater in high-pressing rats compared to low-pressing rats despite similar changes in DAT function. In conclusion, the present manuscript is the first to describe transporter function and METH/AMPH levels after self-administration in rodents. These data provide a foundation to investigate complex questions including how the response of dopaminergic systems to METH self-administration contributes to contingent-related processes such as dependence.

Figure 1

METH self-administration patterns vary among rats. Rats were sorted based on active lever pressing behavior. Rats self-administered METH (0.06 mg/infusion) or saline (10 µL) for 5 d (4 h/d). See Results for description of LP and HP rats.

Figure 2

METH self-administration decreased DAT (A) and VMAT-2 (B) function. Rats self-administered METH (0.06 mg/infusion) or saline (10 µL) for 5 d (4 h/d), and were sacrificed 1 h after the final session. Columns represent the mean (+SEM). *p < 0.05 vs. saline.