title: Blockade of TrkB receptors in the nucleus accumbens prior to heterotypic stress alters corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway.
abstract: Inhibition of stress-induced elevations in brain-derived neurotrophic factor (BDNF) or its primary receptor tyrosine-related kinase B (TrkB) within the reward pathway may modulate vulnerability to anxiety and mood disorders. The current study examined the role of BDNF/TrkB signaling on biochemistry and behavior under basal conditions and following exposure to a 10-day heterotypic stress paradigm in male rats. Effects of intra-accumbal administration of TrkB antagonist ANA-12 (0.25μg/0.5μl/min) on anxiety, and expression of Trk-B, corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway were determined. Notably, ANA-12 attenuated anxiety-like behavior in stress rats while increasing anxiety in the non-stress group in the elevated plus maze (EPM). At the neurochemical level, ANA-12 blocked the increased vGluT2 and CRH expressions in the hypothalamic PVN and basolateral amygdala in stress rats, while it enhanced vGluT2 and CRH expressions in non-stress rats. ANA-12 also showed state-dependent effects at the NAc core, attenuating TrkB-ir in non-stress rats while reversing reduced expression in stressed rats. At the cingulate cortex, ANA-12 normalized stress-induced increase in TrkB expression. Notably, ANA-12 showed region-specific effects on GR-ir at the NAc core and shell, with increased GR-ir in non-stress rats, although the drug attenuated stress-induced GR-ir expression only in the core portion of the NAc, while having no impact at the cingulate cortex. Elevated blood CORT levels post-stress was not influenced by ANA-12 treatment. Together, these findings suggest that BDNF-mediated TrkB activation exerts differential impact in regulating emotional response under basal and stress conditions.
authors.affiliation: Behavioural Neuroscience Group, School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, ON, Canada.
authors.forename: Idu
authors.initials: I
authors.lastname: Azogu
authors.affiliation: Behavioural Neuroscience Group, School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, ON, Canada. Electronic address: hplamond@uottawa.ca.
authors.forename: Helene
authors.initials: H
authors.lastname: Plamondon
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000037:antagonists & inhibitors*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism*
chemical_list: C559317:ANA 12 compound; D001381:Azepines; D001549:Benzamides; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D050599:Vesicular Glutamate Transport Protein 2; D003346:Corticotropin-Releasing Hormone; D020813:Receptor, trkB
keywords: ANA-12; BDNF; Emotionality; HPA axis; Heterotypic stress; Nucleus accumbens; TrkB