Neuroadaptations in the dopaminergic system after active self-administration but not after passive administration of methamphetamine

Methamphetamine is a strong and long-lasting stimulant that can be easily s ynthesized and is effective when taken either orally, intravenously, or smo ked as 'ice'. Due to it's escalating abuse, a clear need exists for laborat ory procedures to evaluate motivational components of methamphetamine abuse and their underlying neurobiological mechanisms. In the present experiment , we utilized a 'yoked' procedure in which rats were run simultaneously in groups of three, with two rats serving as yoked controls which received an injection of either 0.1 mg/kg methamphetamine or saline which was not conti ngent on responding each time a response-contingent injection of 0.1 mg/kg methamphetamine was self-administered by the third paired rat. Rats that ha d actively self-administered methamphetamine for 5 weeks and were then with drawn from methamphetamine for 24 h showed marked decreases in somatodendri tic dopamine D-2 autoreceptors levels in the ventral tegmental area (34%) a nd medial (31%) and dorsal (21%) part of the substantia nigra zona compacta with a corresponding down-regulation of dopamine D-1 receptors in the shel l of the nucleus accumbens (15%), as measured by in vitro quantitative auto radiography. Since the decreases in levels of dopamine D-1 and D-2 receptor s which occurred in rats self-administering methamphetamine did not occur i n littermates that received either yoked injections of methamphetamine or s aline, these changes likely reflect motivational states that were present w hen methamphetamine injection depended an active drug self-administration b ehavior. (C) 1999 Elsevier Science B.V. All rights reserved.