STRIATAL ACETYLCHOLINE-RELEASE CORRELATES WITH BEHAVIORAL SENSITIZATION IN RATS WITHDRAWN FROM CHRONIC AMPHETAMINE

Stimulant sensitization is defined as an enhancement of the behavioral response to drug after repeated drug exposure. We have examined the r elation between the expression of behavioral sensitization and the rel ease of the striatal neurotransmitters acetylcholine (ACh) and dopamin e (DA). Rats were treated with amphetamine (4 mg/kg i.p., b.i.d.) for 12 days, The behavioral response to amphetamine challenge was assessed during the chronic treatment, al short withdrawal (2 days) and at lon g withdrawal (2-3 wk) from the drug. Neurochemical responses to amphet amine challenge were assessed in separate groups of rats at the two wi thdrawal timepoints using in vivo microdialysis, The expression of beh avioral sensitization in response to a low challenge dose of amphetami ne (0.5 mg/kg) was only observed after long withdrawal; indeed, tolera nce was observed at the short withdrawal timepoint. In contrast, sensi tization of the behavioral response to challenge with 4 mg/kg amphetam ine developed progressively over the course of drug treatment and cont inued to increase throughout withdrawal. Striatal ACh release was enha nced by amphetamine challenge (4 mg/kg) in the chronically treated ani mals and this response also was greater at long withdrawal vs, short w ithdrawal. However, amphetamine administration had no net effect on st riatal ACh release in animals previously given chronic saline injectio ns. Amphetamine challenge increased striatal DA release but this respo nse did not differ between drug-or saline-treated animals at either wi thdrawal timepoint. Thus, an enhancement of the drug-induced stimulati on of striatal ACh release correlates with the temporal profile of the expression of behavioral sensitization to amphetamine. In contrast, a mphetamine-induced DA release does not appear to correlate with the ex pression of behavioral sensitization in the same manner.