MICRODIALYSIS ASSESSMENT OF METHAMPHETAMINE-INDUCED CHANGES IN EXTRACELLULAR NEUROTENSIN IN THE STRIATUM AND NUCLEUS-ACCUMBENS

Stimulants of abuse such as cocaine and methamphetamine (METH) have dr amatic effects on tissue neurotensin (NT) levels in the striatum and n ucleus accumbens. Presumably these effects are due to the ability of s uch drugs to increase dopamine transmission. Because changes in dopami ne activity appear to influence NT systems, we examined the effects of increasing doses of METH on extracellular NT levels in the medial str iatum and nucleus accumbens using in vivo microdialysis in conscious r ats. At the lowest dose tested (0.5 mg/kg), METH almost doubled the ex tracellular concentration of NT in both regions. When the dose of METH was increased to 5.0 mg/kg, extracellular NT concentration was elevat ed, but only to approximately 150% of control. At the highest dose exa mined (15.0 mg/kg), extracellular NT was not altered compared to pretr eatment control levels. The role of DA D-1 and D-2 receptors in mediat ing these effects was determined by combining specific antagonists wit h the low dose of METH. The D-1 antagonist SCH 23390 blocked the METH- induced increase in extracellular NT levels in the striatum, but not i n the nucleus accumbens. Pretreatment with the D-2 antagonist, eticlop ride, blocked the increase in extracellular NT in both regions. Change s in striatal NT extracellular levels after a single METH injection we re compared to the alterations in tissue NT levels following multiple administrations of the same doses of METH. Tissue levels were signific antly elevated with 5 or 15 mg/kg METH in the medial, but not the late ral, striatum. There was not a clear correlation observed between the METH effects on striatal NT tissue levels and extracellular NT concent ration.