Self-injurious behavior (SIB) is a major clinical problem among mentally retarded children and adults. Despite considerable research effort, the determinants of SIB remain largely unknown, and currently used therapeutic measures have had limited success. The lack of progress toward understanding and treating SIB can be attributed, in part, to a paucity of research concerning the neurobiological basis of this behavior. Studies with both animals and humans suggest that this behavior is related to aberrant neurochemical processes in the substantia nigra and its output stations. The major objective of the studies outlined in this proposal is to examine the role played by each of these structures in SIB produced by microinjecting the GABA agonist muscimol into the substantia nigra of rats. This will be accomplished by examining the effect of lesioning discrete brain regions on muscimol-induced SIB. It is hypothesized that the brain areas under investigation play a role in the production of SIB by mediating one of two processes: 1) a tendency toward perseverative motor acts, and 2) alterations in nocieceptive thresholds. Each of these processes will be investigated in brain regions found to regulate muscimol-induced SIB. A final objective of this proposal is the development of an animal model of SIB that involves alterations in dopamine systems in the basal ganglia. Recent evidence suggests that perturbations in striatal dopamine function are related to the SIB seen in Lesch-Nyhan patients. Studies are planned to determine whether SIB produced by enhancing dopamine transmission in the striatum is mediated by the substantia nigra.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Unknown (R23)
Project #
7R23HD021560-01
Application #
3448357
Study Section
Neurology A Study Section (NEUA)
Project Start
1985-09-01
Project End
1987-05-31
Budget Start
1985-09-01
Budget End
1986-05-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Louisiana State University A&M Col Baton Rouge
Department
Type
Schools of Arts and Sciences
DUNS #
075050765
City
Baton Rouge
State
LA
Country
United States
Zip Code
70803
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Baumeister, A A; Hawkins, M F; Anderson-Moore, L L et al. (1988) Effects of bilateral injection of GABA into the substantia nigra on spontaneous behavior and measures of analgesia. Neuropharmacology 27:817-21
Baumeister, A A; Anticich, T G; Hawkins, M F et al. (1988) Evidence that the substantia nigra is a component of the endogenous pain suppression system in the rat. Brain Res 447:116-21
Baumeister, A A; Hawkins, M F; Anticich, T G et al. (1987) Bilateral intranigral microinjection of morphine and opioid peptides produces antinociception in rats. Brain Res 411:183-6
Baumeister, A A; Frye, G D; Moore, L L (1987) An investigation of the role played by the superior colliculus and ventromedial thalamus in self-injurious behavior produced by intranigral microinjection of muscimol. Pharmacol Biochem Behav 26:187-9