Adrenoreceptor Antagonist Treatment Influences Recovery of Learning Following Medial Septal Lesions and Hippocampal Sympathetic Ingrowth

Previous studies have demonstrated that in male rats hippocampal sympathetic ingrowth (HSI), which is induced by medial septal lesions (MS), is detrimental to recovery of spatial learning. The present study was performed in an attempt to determine if this effect was mediated through adrenergic receptor activity. Adult male Sprague-Dawley rats underwent training on a modified version (i.e., 4 arms baited) of a radial-8-arm maze task. Following attainment of learning criterion animals underwent one of three surgical procedures: CON (sham surgeries); MSGx (MS + superior cervical ganglionectomy--to prevent HSI); MS (MS + sham ganglionectomy). Reacquisition trials were performed in the same manner as initial acquisition except animals were treated with vehicle, propranolol (20 mg/kg), or phentolamine (20 mg/kg) 30 minutes prior to testing. As expected, vehicle-treated MS animals took longer to reacquire the task than MSGx animals, who were in turn more impaired than CON animals. Propranolol (beta-adrenergic antagonist) treatment impaired performance of both the MS and MSGx group, but did not alter the CON group. Phentolamine (alpha-adrenergic antagonist) increased the number of trials to reattain criterion in the CON group, had no effect in the MSGx group, and markedly improved performance in the MS group. The results suggest that HSI mediates its detrimental effects through alpha-receptors, while beta-blockade, in the setting of brain injury, is detrimental to performance regardless of the presence or absence of HSI.