| Before a treatment for METH addiction can be developed more research must be done to characterize the pharmacological properties of the drug. One strategy to accomplish this goal is to compare METH to the better-understood psychostimulant amphetamine (AMPH). Using the technique of in vivo microdialysis on rats, extracellular levels of dopamine (DA) and glutamate (GLU) were measured in the nucleus accumbens (NAC) and prefrontal cortex (PFC) after administration of METH or AMPH. Several behavioral measures that involve DA and GLU in the NAC and PFC were also assessed. Locomotor activity was measured after administration of METH or AMPH. Working memory, hypophagia, tolerance, and extinction were measured using a T-maze. METH and AMPH raised DA levels in the NAC and PFC. Even though METH and AMPH did not differ in raising DA levels in the NAC, AMPH had a greater effect than METH on DA levels in the PFC. Desipramine, a selective NE transporter (NET) blocker, attenuated the effect of AMPH on PFC DA levels while synergistically increasing the effect of METH on PFC DA levels. METH, but not AMPH, raised GLU levels in the PFC. AMPH, but not METH, raised GLU levels in the NAC. Both METH and AMPH stimulated locomotor activity with similar potency, however, AMPH was more efficacious than METH. Pretreatment with GLU antagonists into the NAC blocked this difference in efficacy. Both METH and AMPH produced dose related bimodal effects on working memory, but AMPH was more potent than METH. METH, but not AMPH, interfered with extinction. These results indicate several previously unknown differences between METH and AMPH. It is suggested that AMPH stimulates DA release in the PFC through NET, while METH has less interaction with NET. It is also proposed that AMPH is more effective than METH at stimulating locomotor activity by further facilitating locomotor activity through NAC GLU release. Both METH and AMPH differ in several behavioral functions of the PFC, perhaps due to the differences between METH and AMPH on DA and GLU levels in the PFC. The implications for treating METH addiction are discussed. |
