ANXIOLYTIC TREATMENTS--NEUROPHARMACOLOGICAL MECHANISMS

描述（改编自申请人摘要）：基于工作

DESCRIPTION (Adapted from the Applicant's Abstract): Based upon work conducted by the investigator and in other laboratories, there are four distinct clinically effective anxiolytic treatments that exert robust anticonflict effects in rodent models for anxiety: (1) acute benzodiazepine or barbiturate treatment, (2) chronic buspirone treatment, (3) chronic antidepressant treatment and (4) chronic clonidine treatment. The present studies are designed to examine the behavioral, neuroanatomical, and neurotransmitter mechanism for these diverse anxiolytic treatments. Studies in Specific Aim 1 are designed to examine the behavioral mechanisms for these anxiolytic treatment effects. First, the effects of these anxiolytic treatments will be determined (in some instances, re-determined) in the elevated plus maze conflict task, a non-shock conflict task which has been extensively validated as an animal model for anxiety. Second, shock sensitivity testing following the various anxiolytic treatments will be conducted to confirm that the anticonflict effects observed in the conditioned suppression of drinking (CSD) procedure are not secondary to antinociceptive effects. Studies in Specific Aim 2 will determine the importance of two limbic postsynaptic sites (central nucleus of the amygdala (CNA) and lateral septum (LS)) for the expression of the various anxiolytic treatment effects. In these studies, the effects of these anxiolytic treatments will be determined following electrolytic lesions of either the CNA, LS, or both structures. Studies in Specific Aim 3 will determine the importance of the monoamine neurotransmitters norepinephrine (NE) and 5-hydroxytryptamine (5-HT) for the expression of the anticonflict effects of the various treatments. In these studies, the effects of the anxiolytic treatments will be determined following chemical (6-OHDA, 5,7-DHT) or electrolytic lesions of NE-containing neurons in the locus ceruleus (LC), 5-HT-containing neurons within the dorsal raphe nucleus (DRN), or neurons in both sites. Studies in Specific Aim 4 will determine how these anxiolytic treatments affect the discharge rate, pattern, and drug sensitivity of single LC-NE or DRN-5-HT neurons. These studies will use standard electrophysiological recording procedures in anesthetized rats which have received the various anxiolytic treatments. Together, the proposed studies will begin to address both presynaptic and postsynaptic mechanism underlying the expression of a diverse group of anxiolytic treatments.