Asymmetrical locomotor response to unilateral cortical injections of DSP-4

The role of norepinephrine depletion in the lateralized production of spontaneous hyperactivity was assessed by unilateral fronto-cortical injections of either 10 or 20 micrograms of the noradrenergic neurotoxin, DSP-4 (N-2-chlorethyl-N-ethyl-bromobenzylamine hydrochloride). Ten micrograms of DSP-4 produced significant hyperkinesis only when injected into the right hemisphere. A 20 micrograms dose produced hyperactivity when injected into either hemisphere. DSP-4 injections resulted in significant NE and ipsilateral and contralateral 5HT depletions in the frontal cortex. The 20 micrograms right hemispheric injection significantly increased both DOPAC and DA levels in the contralateral caudate in a manner unrelated to behavior. These findings, in conjunction with results from previous neurotoxin studies, support a hypothesis of greater relative sensitivity to injury of right hemispheric NE terminal fields compared with injury to left hemispheric fields as demonstrated by spontaneous hyperactivity.