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 nucleus accumbens (NAc) of freely moving rats after intraperitoneal administration of the muscarinic receptor antagonist scopolamine (0.5 mg/kg) or vehicle. Simultaneously, behavior was monitored. The administration of scopolamine induced an increase in extracellular ACh levels in the NS, which reached a maximum of about 185% within one hour after injection and returned to baseline values about three hours after injection. In the NAc, an increase of similar time-course was observed; however, this increase reached a maximum of 250%, which was significantly higher than the one observed in NS. These changes in ACh levels were accompanied by enhanced locomotion, rearing and grooming; however, the behavioral changes were of shorter time-course than those of extracellular ACh. The injection of vehicle did not affect ACh levels in NS, but induced a significant increase (60%) in the NAc. The levels of behavioral activity after vehicle injection did not differ from pre-injection levels. These results suggest, that the cholinergic systems in the NAc and NS are differently affected by peripheral administration of both scopolamine and vehicle. The differential effects of scopolamine in NS and NAc could reflect pharmacodynamic differences between these two striatal brain areas, perhaps due to a higher density of cholinergic interneurons or muscarinic autoreceptors in the NAc in comparison to the NS. However, the increase of extracellular ACh observed after vehicle 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 might be an additive effect of the drug with that of the injection procedure.