This project investigates """"""""locomotor stereotypy"""""""" exhibited by amphetamine-treated rats. Locomotor stereotypy is defined as repetition of a pattern of locomotion in an open field that is, the rat frequently retraces its steps. Locomotor stereotypy is an important but little studied component of the behavioral response to amphetamine in rats. The ability to describe and quantify locomotor stereotypy provides a much more sophisticated tool for behavior analysis that an is currently available. The health relatedness of the project lies in the widespread use of the behavioral effects of amphetamine in rats as a model of dopamine (DA) activity in the brain. For example, a drug which blocks the behavioral effects of amphetamine may be a useful antipsychotic; a neuropeptide which alters the behavioral effects of amphetamine may influence dopaminergic transmission in some way, and so on. The long-term objective of this research is to combine behavioral, pharmacological and neurochemical data into a model of rat locomotor behavior in an open field. The more immediate goal is to determine whether locomotor stereotypy is produced exclusively by drugs acting on DA systems in the brain.
The specific aims are 1) To refine the model by adding a means of quantifying stereotypic raring. 2) To determine the effects of repeated exposure to the open field on locomotor stereotypy. 3) To characterize the effects of indirect DA agonist apomorphine on locomotor stereotypy. 4) To characterize mine the effect of scopolamine, a cholinergic antagonist which indirectly modulates DA release, on locomotor stereotypy. 6) To determine the effect of caffeine, a relatively nonspecific stimulant, on locomotor stereotypy. 7) To determine the effect of micro-infusion of amphetamine and apomorphine into the nucleus accumbens or caudate nucleus on locomotor stereotypy. To accomplish these aims, the rats will be injected, placed in the center of an open field, and videotaped. The route through the open field will be traced onto a schematic of the open field by trained observers. From these data the following dependent variables are calculated: lines crossed (an index of general activity), rears, stereotypic rears, (quantifies locomotor stereotype) and proportions of trip types (describes the route of locomotion). The first two aims refine the procedure. The outcome of the remaining experiments will determine whether stereotypy can be used as a model of DA activity on the brain.
| Fritts, M E; Mueller, K; Morris, L (1998) Locomotor stereotypy produced by dexbenzetimide and scopolamine is reduced by SKF 83566, not sulpiride. Pharmacol Biochem Behav 60:639-44 |
| Fritts, M E; Mueller, K; Morris, L (1997) Amphetamine-induced locomotor stereotypy in rats is reduced by a D1 but not a D2 antagonist. Pharmacol Biochem Behav 58:1015-9 |
| Mueller, K (1993) Locomotor stereotypy is produced by methylphenidate and amfonelic acid and reduced by haloperidol but not clozapine or thioridazine. Pharmacol Biochem Behav 45:71-6 |
| Mueller, K; Whiteside, D A (1990) Enkephalin prevents CCK-induced enhancement of amphetamine-induced locomotor stereotypy. Brain Res 513:119-24 |
| Mueller, K; Peel, J L (1990) Scopolamine produces locomotor stereotypy in an open field but apomorphine does not. Pharmacol Biochem Behav 36:613-7 |
| Mueller, K; Kunko, P M; Whiteside, D et al. (1989) Time course of amphetamine-induced locomotor stereotypy in an open field. Psychopharmacology (Berl) 99:501-7 |
