Enhanced muscimol-induced behavioral responses after 6-OHDA lesions: relevance to susceptibility for self-mutilation behavior in neonatally lesioned rats

Adult rats lesioned with 6-hydroxydopamine (6-OHDA), either as neonates or as adults, demonstrated increased turning, compared to unlesioned controls, when muscimol was unilaterally microinjected into the substantia nigra reticulata (SNR). At the higher doses of muscimol, the lesioned rats were so intensely lateralized that circling was impeded. These data suggest a functional supersensitivity of receptors associated with GABA function in the SNR of 6-OHDA-lesioned rats. When 30 ng muscimol was administered bilaterally into the SNR, self-mutilation behavior (SMB) was observed in 2/11 of the control unlesioned rats, in 0/8 adult 6-OHDA-lesioned rats, and in 11/11 of the neonatally-lesioned rats tested. The ability of muscimol to produce SMB in the rats lesioned as neonates was dose related. Behavioral observations indicated that behaviors associated with SMB (self-biting and taffy pulling) were present in neonatal, but not adult lesioned rats. Behavioral responses to dopamine agonist administration were also different between rats lesioned as neonates and those lesioned as adults with 6-OHDA. These data support the view that lesions of dopaminergic neurons cause an increased functional responsiveness of receptors acted upon by muscimol in the SNR, and that the increased susceptibility for SMB in neonatally lesioned rats is determined by neurons distal to the GABA receptor complex in the SNR.