Multiple anxiogenic drugs recruit a parvalbumin-containing subpopulation of GABAergic interneurons in the basolateral amygdala.
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., increases c-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-HT(2A) 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-HT(2C/2A) receptor agonist m-chlorophenyl piperazine (mCPP), the adenosine receptor antagonist caffeine, the α(2)-adrenoreceptor antagonist yohimbine and the partial inverse agonist at the benzodiazepine allosteric site on the GABA(A) 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 BLA were 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 vehicle-injected controls. Together, these data suggest that the PV/5-HT(2A) receptor expressing GABAergic interneurons in the basolateral amygdala are part of a DR-basolateral amygdala neuronal circuit modulating anxiety-states and anxiety-related behavior.
Hale
Matthew W
MW
Department of Integrative Physiology and Center for Neuroscience, University of Colorado, Boulder, CO, 80309-0354, USA. matthew.hale@colorado.edu
Johnson
Philip L
PL
Westerman
Alex M
AM
Abrams
Jolane K
JK
Shekhar
Anantha
A
Lowry
Christopher A
CA
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D007395:Interneurons / Q000187:drug effects*; D008297:Male; D010320:Parvalbumins / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D002243:Carbolines; D010320:Parvalbumins; D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D044402:Receptor, Serotonin, 5-HT2A; D015016:Yohimbine; D002110:Caffeine; D005680:gamma-Aminobutyric Acid; C035874:FG 7142; C015068:1-(3-chlorophenyl)piperazine