Self-injurious behavior in rats produced by intranigral microinjection of GABA agonists

Bilateral injection of the GABA agonist muscimol (10-300 ng) into the caudal substantia nigra (pars reticulata) of rats produced dose-dependent stereotyped gnawing and self-biting. Limiting the opportunity to gnaw on inanimate objects shifted the dose-response curve for muscimol-induced self-injurious behavior (SIB) to the left and increased the maximum incidence of SIB. Microinjection of muscimol (30 ng) into the rostral and caudal regions of the substantia nigra were equally effective in producing SIB, though the incidence of SIB decreased sharply when muscimol was injected 1 mm rostral or caudal to the substantia nigra. Bilateral intranigral injection of THIP (100-1000 ng) and (+/-)baclofen (100-1000 ng) induced a low incidence of SIB. However, neither IP administration of picrotoxin (5 mg/kg) or simultaneous microinjection of (+)bicuculline methiodide (BMI; 300 or 1000 ng) along with muscimol (30 ng) blocked muscimol-induced SIB. In fact, (+)BMI increased the occurrence of self-biting and reduced the latency to onset of SIB. The involvement of GABAergic mechanisms in muscimol-induced SIB is discussed.