LOCUS COERULEUS, STROKE, AND ANTIDEPRESSANTS

Experiments are proposed to study the effects of experimental stroke and administration of antidepressant drugs on neurotransmission in the noradrenergic-locus coeruleus (NE LC) system. Recordings from single NE-LC neurons in anesthetized rats will examine the effects of middle cerebral artery ligation and acute or chronic administration of desipramine or phenelzine, on the soma excitability, responsiveness to noxious sensory stimuli, and post-excitatory inhibition of these cells. Similar recordings in unanesthetized behaving rats will determine the effects of these treatments on the spontaneous discharge of NE-LC neurons during naturally occurring behaviors and stages of the sleep-waking cycle, as well as their responsiveness to non-noxious sensory stimuli. Electrical stimulation of locus coeruleus, or iontophoresis of norepinephrine, will be used to test the effects of these same treatments on the postsynaptic responsiveness of cells in the parietal cortex and hippocampus to activity in the NE-LC system. The long-term objectives of this research are to determine the effects of stroke and of antidepressant treatment on neurotransmission in the NE-LC system by examining changes induced in both pre- and postsynaptic elements. Such data will be the first of their kind in examining stroke, and some of the first on antidepressants and the NE-LC system. These experiments may provide insights into mechanisms involved in affective disorders that often follow stroke, and further elucidate the role of the NE-LC system in the clinical effectiveness of antidepressant treatment of such disorders.