Discriminative stimulus effects of methamphetamine and in vivo microdialysis in rats

Abstract

The present studies were conducted to examine the relationship between discriminative stimulus effects of MA and its ability to increase extracellular levels of DA in the n. accumbens (nACC) shell. Fist, the behavioral effects of cumulatively administered MA, cocaine (COC), and related stimulants were determined in rats trained to discriminate IP injections of MA (0.3 or 1.0 mg/kg) from saline. In other studies, in vivo microdialysis was used to determine the effects of cumulatively administered MA and COC on extracellular DA levels in the nACC shell. d-Amphetamine, COC, GBR 12909, methylphenidate and AM 2547 produced dose-related and full substitution for 0.3 mg/kg MA. In contrast, comparable doses of COC, GBR 12909, methylphenidate and AM 2547 did not fully mimic the effects of 1.0 mg/kg MA. In microdialysis studies, MA (0.3 – 3 mg/kg) and COC (3 – 30 mg/kg) produced a dose-dependent increase in DA efflux in the nACC shell to approximate maxima of, respectively, 1700% and 550% of control values. In 1.0 mg/kg MA-trained rats, the ED50 dose of MA (0.34 mg/kg) and cocaine (3.98 mg/kg) produced approximately 340% and 210% increases in DA, respectively. In 0.3 mg/kg MA-trained rats, the ED50 dose of MA (0.11 mg/kg) and cocaine (3.03 mg/kg) produced approximately 220% and 200% increases DA levels, respectively. Taken together, these results support a prominent role for dopamine in MA-like discriminative-stimulus effects.