ELECTROPHYSIOLOGICAL ACTIONS OF NEUROPEPTIDE-Y AND ITS ANALOGS - NEW MEASURES FOR ANXIOLYTIC THERAPY

Neuropeptide Y (NPY) has neuromodulatory actions on multiple brain fun ctions including endocrine, behavioral, and circadian processes. Behav ioral studies suggest that NPY is a potent anxiolytic; however, little is known about how NPY affects general arousal and/or attention state s. The present study evaluated the effects of NPY on spontaneous brain activity as well as auditory processing by using electrophysiological measures. Electroencephalographic (EEG) and event-related potentials (ERPs) were obtained in awake animals after intracerebroventricular ad ministration of NPY (1.0, 3.0 nmol) and two of its analogs, active at YI (1.0, 3.0 nmol) and Y2 (1.0, 3.0 nmol) receptor sites. NPY was foun d to produce dose-related effects on electrophysiological measures. Sp ectral analyses of the EEG revealed that NPY produced slowing of delta activity (1-2 Hz) in the frontal cortex and high frequency theta acti vities (6-8 Hz) concomitant with a speeding up of low frequency theta (4-6 Hz) in cortex, hippocampus, and amygdala. At higher doses (3.0 nm ols) in addition to shifts infrequency, EEG power was also significant ly reduced in all frequencies (0.5-50 Hz) in cortex, and in the higher frequencies (8-32 Hz) in the amygdala. The Y1 and Y2 agonists had a s omewhat different profile of EEG effects than the parent compound. At the I nmol dose both agonists were found to produce selective depressi ons in power in the hippocampus. The 3.0 nmols dose of the Y1 agonist produced decreases in EEG stability, an effect commonly produced by an xiolytic drugs, whereas the Y2 agonist produced increases in EEG stabi lity in cortex and amygdala. Auditory processing, as assessed by ERPs, was affected most significantly in the frontal cortex where dose-depe ndent decreases in the N1 component of the ERP, a finding also commonl y seen after anxiolytics, was found. YI and Y2 agonists were also foun d to significantly reduce the amplitude of the N1 component of the ERP but less so than the parent compound. The electrophysiological and be havioral profiles of NPY and the Y1 agonist resembles those of anxioly tics such as ethanol and benzodiazepines. Taken together these data su ggest that electrophysiological measures of the actions of this peptid e system may represent a new potentially useful assay for the developm ent of anxiolytic drugs. (C) 1997 American College of Neuropsychopharm acology.