Bilateral intrahippocampal NAC61–95 effects on behavior and moderation with l-NAME treatment

Residues 61–95 of the non-amyloid component (NAC61–95) domain of α-synuclein are responsible for the aggregation and neurotoxicity of this protein. This study evaluated the effect of N(ω)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor, on the behavior of rats bilaterally injected into the CA3 area of the dorsal hippocampus with aggregated NAC61–95. Twenty-four male Sprague–Dawley rats were trained to respond under an alternating-lever cyclic-ratio (ALCR) operant schedule. When responding was stable, 12 rats were injected bilaterally into the CA3 area of the hippocampus with aggregated NAC61–95 (5 μl per side; concentration 10−4 M), the remaining 12 rats were similarly injected with sterile water (SW), six of the NAC61–95 injected rats and six of the SW injected rats were treated for 90 days post-injections with 0.05 mg/ml l-NAME in drinking water available ad libitum. Treatment with l-NAME alleviated NAC61–95-induced behavioral deficits, indicated through the measurement of lever switching errors and incorrect lever perseverations under the ALCR schedule, and reduced the number of activated astrocytes proximal to the injection sites.