DIFFERENT EFFECTS OF SCOPOLAMINE ON EXTRACELLULAR ACETYLCHOLINE LEVELS IN NEOSTRIATUM AND NUCLEUS-ACCUMBENS MEASURED IN-VIVO - POSSIBLE INTERACTION WITH AVERSIVE-STIMULATION

The in vivo microdialysis technique was used to measure extracellular concentrations of acetylcholine (ACh) in the neostriatum (NS) and nucl eus accumbens (NAc) of freely moving rats after intraperitoneal admini stration of the muscarinic receptor antagonist scopolamine (0.5 mg/kg) or vehicle. Simultaneously, behavior was monitored. The administratio n of scopolamine induced an increase in extracellular ACh levels in th e NS, which reached a maximum of about 185% within one hour after inje ction and returned to baseline values about three hours after injectio n. In the NAc, an increase of similar time-course was observed; howeve r, this increase reached a maximum of 250%, which was significantly hi gher than the one observed in NS. These changes in ACh levels were acc ompanied by enhanced locomotion, rearing and grooming; however, the be havioral changes were of shorter time-course than those of extracellul ar ACh. The injection of vehicle did not affect ACh levels in NS, but induced a significant increase (60%) in the NAc. The levels of behavio ral activity after vehicle injection did not differ from pre-injection levels. These results suggest, that the cholinergic systems in the NA c and NS are differently affected by peripheral administration of both scopolamine and vehicle. The differential effects of scopolamine in N S and NAc could reflect pharmacodynamic differences between these two striatal brain areas, perhaps due to a higher density of cholinergic i nterneurons or muscarinic autoreceptors in the NAc in comparsion to th e NS. However, the increase of extracellular ACh observed after vehicl e injection suggests that factors such as aversive stimulation through the injection procedure can increase ACh release in the NAc and that such a mechanism can interact within the action of scopolamine. Thus, the stronger action of scopolamine on extracellular ACh in the NAc mig ht be an additive effect of the drug with that of the injection proced ure.