On the Problem of Distant Lesions in Behavioual Studies Utilizing Kainic Acid

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This role of the dorsal striatum in d-amphetamine-induced motor responses has been re-investigated using kainic and ibotenic acid lesions. In accordance with previous observations, bilateral stereotaxic injections of kainic acid into the striatum resulted in large increases in d-amphetamine-induced locomotor activity. Intraventricular injections of kainic acid, which cause insignificant damage to the striatum, while producing a pattern of distant lesions that are similar to those found after intrastriatal injections, also enhanced the locomotor stimulant effects of amphetamine but to a smaller extent. These results indicate that the distant, extrastriatal lesions that are found after intrastriatal injections of kainic acid contribute to the enhanced locomotor stimulant effects of d-amphetamine. However, damage to the striatum itself is also partly responsible for the potentiation of amphetamine-induced locomotor activity because bilateral ibotenic acid lesions of the striatum, which do not cause distant, extrastriatal lesions, also enhanced this effect of amphetamine. Unilateral intrastriatal injections of kainic acid resulted in ipsilateral turning after d-amphetamine. This observation is not compatible with the hypothesis that kainic acid lesions of the striatum interrupt a striato-nigral negative feedback loop. The discrepancies obtained using unilateral and bilateral excitotoxic lesions of the striatum indicate that at present it is not possible to provide a unified theoretical framework within which to account for the effect of striatal lesions on amphetamine-induced motor behaviors. In contrast to previous findings with kainic acid, bilateral ibotenic acid lesions of the dorsal striatum did not enhance spontaneous locomotor activity during the dark phase of the day-night cycle. This result indicates that the previous finding of increased nocturnal activity after intrastriatal injections of kainic acid is best attributed to the non-striatal, distant lesions produced by this toxin. Some advantages of ibotenic acid over kainic acid in behavioral studies are discussed.