ABSTRACT
Recently, it was demonstrated that the priming stimulation effect (PSE) of intracranial self-stimulation (ICSS) with the runway method can be used as a model system to study the motivation that contributes to specific behaviors. It was postulated that these behaviors could be used to compare the effects of various drugs on the mechanism of motivation. In the present study, the influences of nicotine, methyllycaconitine (alpha7 nicotine-receptor antagonist), and dihydro-beta-erythroidine (alpha4beta2 nicotine-receptor antagonist) on motivation were examined using the runway method for ICSS. Electrodes were implanted into the medial forebrain bundle of Wistar rats. The rats ran to the goal lever to get the reward (50 - 200 microA, 0.2 ms, 60 Hz) and pretrial electric stimulation (priming stimulation) in the medial forebrain bundle was performed. The experiment measured the running time from the start box until the rat pressed the goal lever for the reward stimulation. Under these reward and priming stimulation conditions, nicotine (0.2 mg/kg) induced a significant increase in running speed. The nicotine receptor antagonist alpha4beta2 rather than alpha7 showed a dose-dependent antagonistic action on the effect of nicotine on running speed. These results demonstrate that nicotine enhances the running speed towards the goal lever via alpha4beta2 nicotinic receptors and suggest that alpha4beta2 nicotinic receptors influence the brain mechanism of motivation.
Subject(s)
Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Receptors, Nicotinic/drug effects , Self Stimulation/drug effects , Aconitine/administration & dosage , Aconitine/analogs & derivatives , Aconitine/pharmacology , Animals , Behavior, Animal/drug effects , Conditioning, Operant/drug effects , Dihydro-beta-Erythroidine/administration & dosage , Dihydro-beta-Erythroidine/pharmacology , Dose-Response Relationship, Drug , Electric Stimulation , Male , Medial Forebrain Bundle/drug effects , Motivation , Nicotinic Antagonists/administration & dosage , Nicotinic Antagonists/pharmacology , Rats , Rats, Wistar , Reward , RunningABSTRACT
We investigated the relationship between the degree of spatial memory impairment in an 8-arm radial maze and the changes in the contents of acetylcholine (ACh) and noradrenaline (NA) in the dorsal and ventral hippocampus and the frontal cortex, along with histological changes in kaolin-induced hydrocephalic rats. Kaolin-induced hydrocephalic rats were divided into three groups (non-impaired, impaired and severely impaired) according to the degree of impairment in a radial maze. Thirty percent of the hydrocephalic rats could not solve a radial maze (severely impaired group), while the remaining hydrocephalic rats could (non-impaired rats in the standard task). Forty percent of the non-impaired rats in the standard task failed to solve the delayed-response task (impaired group), whereas the remaining rats were able to solve it (non-impaired group). A positive correlation was observed between the impairment of spatial memory and ventricular dilatation. The ACh content in the dorsal and ventral hippocampus, and the NA content in the ventral hippocampus were decreased in the severely impaired group. Moreover, the NA content in the ventral hippocampus was decreased in the impaired group. These results suggest that the impairment of spatial memory in kaolin-induced hydrocephalic rats is associated with dysfunction of the hippocampal cholinergic and noradrenergic systems.
