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Progress in Neuro-Psychopharmacology & Biological Psychiatry
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Multiple anxiogenic drugs recruit a parvalbumin-containing subpopulation of GABAergic interneurons in the basolateralamygdala
Matthew W. Hale a,⁎, Philip L. Johnson b,c, Alex M. Westerman a, Jolane K. Abrams b, Anantha Shekhar c, Christopher A. Lowry a,b
a b c
Department of Integrative Physiology and Center for Neuroscience, University of Colorado, Boulder, CO, 80309-0354, USA Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, BS1 3NY, UK Department ofPsychiatry and Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA
a r t i c l e
i n f o
a b s t r a c t
The basolateral amygdala is a nodal structure within a distributed and interconnected network that regulates anxiety states and anxiety-related behavior. Administration of multiple anxiogenic drugs increases cellular responses (i.e., increasesc-Fos expression) in a subregion of the basolateral amygdala, but the neurochemical phenotypes of these cells are not known. The basolateral amygdala contains glutamatergic projection neurons and several populations of γ-aminobutyric acid-synthesizing (GABAergic) interneurons, including a population of parvalbumin (PV)-expressing GABAergic interneurons that co-express the excitatory 5-HT2A receptor.The role for these PV-expressing GABAergic interneurons in anxiety-states is unclear. In this experiment we examined the effects of multiple anxiogenic drugs including the 5-HT2C/2A receptor agonist m-chlorophenyl piperazine (mCPP), the adenosine receptor antagonist caffeine, the α2-adrenoreceptor antagonist yohimbine and the partial inverse agonist at the benzodiazepine allosteric site on theGABAA receptor, N-methyl-beta-carboline-3-carboxamide (FG-7142), on c-Fos expression in PV-immunoreactive (PV-ir) interneurons in subdivisions of the basolateral amygdala. All drugs with the exception of mCPP increased c-Fos expression in PV-ir neurons in the basolateral amygdaloid nucleus, anterior part (BLA). The numbers of c-Fos-immunoreactive (c-Fos-ir)/PV-ir GABAergic interneurons in the BLAwere positively correlated with the numbers of c-Fos-ir serotonergic neurons in the mid-rostrocaudal dorsal raphe nucleus (DR) and with a measure of anxiety-related behavior. All four drugs increased c-Fos expression in non-PV-ir cells in most of the subdivisions of the basolateral amygdala that were sampled, compared with vehicleinjected controls. Together, these data suggest that the PV/5-HT2Areceptor expressing GABAergic interneurons in the basolateral amygdala are part of a DR-basolateral amygdala neuronal circuit modulating anxiety-states and anxiety-related behavior. Published by Elsevier Inc.
Article history: Received 9 May 2010 Received in revised form 8 July 2010 Accepted 13 July 2010 Available online 18 July 2010 Keywords: Anxiety Basolateral amygdala C-Fos Dorsal raphenucleus Serotonin
1. Introduction Anxiety is a complex emotional state associated with heightened physiological and behavioral arousal (Lowry et al., 2005; Lowry and
Abbreviations: 5-HT2A, serotonin 2A receptor subtype; 5-HT2C, serotonin 2C receptor subtype; ANOVA, analysis of variance; BLA, basolateral amygdaloid nucleus, anterior part; BLP, basolateral amygdaloid nucleus, posterior part; CRF,corticotropinreleasing factor; DAB, 3,3’-diaminobenzidine tetrahydrochloride; DR, dorsal raphe nucleus; DRC, dorsal raphe nucleus, caudal part; DRD, dorsal raphe nucleus, dorsal part; FG-7142, N-methyl-beta-carboline-3-carboxamide; GABA, γ-aminobutyric acid; LaDL, lateral amydaloid nucleus, dorsolateral part; LaVL, lateral amydaloid nucleus, ventrolateral part; LaVM, lateral amydaloid nucleus,...