METHAMPHETAMINE SELECTIVELY DAMAGES DOPAMINERGIC INNERVATION TO THE NUCLEUS-ACCUMBENS CORE WHILE SPARING THE SHELL

Dopaminergic innervation to the nucleus accumbens was investigated fol lowing a neurotoxic regimen of methamphetamine (MA) treatment. Four 10 mg/kg doses of MA were administered s.c. to male Sprague-Dawley rats with a 2 h interval between doses. Rectal temperatures were monitored for the induction of MA-induced hyperthermia. Three days or 2 weeks af ter MA treatment the animals were sacrificed by transcardial perfusion and processed for tyrosine hydroxylase (TH-IR) and glial fibrillary a cidic protein immunoreactivity (GFAP-IR). MA treatment produced a seve re loss of TH-IR throughout the striatum, including the nucleus accumb ens. However, within the nucleus accumbens, there was substantial spar ing of TH-IR in the shell, while in the core immunoreactivity was almo st entirely lost. Furthermore, astrogliosis, as demonstrated by GFAP-I R, was prevalent in the core but present only in sparse patches in the medial and lateral shell. Thus, dopaminergic innervation to the nucle us accumbens core undergoes degeneration following MA treatment, while innervation to the shell is resistant to the neurodegenerative effect s of MA. (C) 1997 Wiley-Liss, Inc.