Francis Rodriguez Bambico1,2, Zhuoliang Li3, Caio Oliveira3, Sean McNeill3, Mustansir Diwan3, Roger Raymond3, José N Nobrega3. 1. Behavioural Neurobiology Laboratory, Campbell Family Mental Health Research Institute and Research Imaging Center, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R82, Canada. fbambico@mun.ca. 2. Department of Psychology, Memorial University of Newfoundland, St John's, NL, A1B 3X9, Canada. fbambico@mun.ca. 3. Behavioural Neurobiology Laboratory, Campbell Family Mental Health Research Institute and Research Imaging Center, Centre for Addiction and Mental Health, Toronto, Ontario, M5T 1R82, Canada.
Abstract
RATIONALE: The ventral tegmental area (VTA) is implicated in the pathophysiology of depression and addictive disorders and is subject to the detrimental effects of stress. Chronic stress may differentially alter the activity pattern of its different subregions along the rostrocaudal and dorsoventral axes, which may relate to the variable behavioral sensitivity to stress mediated by these subregions. OBJECTIVES: Here, chronic stress-exposed rats were tested for depressive-like reactivity. In situ hybridization for zif268 as a marker of neuronal activation was combined with in vivo single-unit recording of dopaminergic neurons to assess modifications in the activity of the rostral VTA (rVTA) and caudal VTA (cVTA). Changes in the expression of stress-responsive glucocorticoid receptors (GR) and brain-derived neurotrophic factor (BDNF) were also assessed. RESULTS: Stress-induced anhedonia-like, hyper-anxious, and passive-like responding were associated with reductions in dopaminergic burst activity in the cVTA and an increase in local GABAergic activity, particularly in GABAA receptor sensitivity. On the other hand, stress increased single-spiking activity, burst activity, and zif268 mRNA levels in the rVTA, which were associated with increased glutamatergic tonus and enhanced GR and AMPA receptor (AMPAR) expression. rVTA and cVTA activity differentially correlated with sucrose preference and passivity measures. CONCLUSIONS: These data demonstrate that the rVTA and cVTA respond differently to stress and suggest that while cVTA activity may be related to passivity-like states, the activity of both subregions appears to be related to anhedonia and the processing of incentive value. These region-dependent abnormalities indicate the multi-modular composition of the VTA, which could provide multiple substrates for different symptom features.
RATIONALE: The ventral tegmental area (VTA) is implicated in the pathophysiology of depression and addictive disorders and is subject to the detrimental effects of stress. Chronic stress may differentially alter the activity pattern of its different subregions along the rostrocaudal and dorsoventral axes, which may relate to the variable behavioral sensitivity to stress mediated by these subregions. OBJECTIVES: Here, chronic stress-exposed rats were tested for depressive-like reactivity. In situ hybridization for zif268 as a marker of neuronal activation was combined with in vivo single-unit recording of dopaminergic neurons to assess modifications in the activity of the rostral VTA (rVTA) and caudal VTA (cVTA). Changes in the expression of stress-responsive glucocorticoid receptors (GR) and brain-derived neurotrophic factor (BDNF) were also assessed. RESULTS: Stress-induced anhedonia-like, hyper-anxious, and passive-like responding were associated with reductions in dopaminergic burst activity in the cVTA and an increase in local GABAergic activity, particularly in GABAA receptor sensitivity. On the other hand, stress increased single-spiking activity, burst activity, and zif268 mRNA levels in the rVTA, which were associated with increased glutamatergic tonus and enhanced GR and AMPA receptor (AMPAR) expression. rVTA and cVTA activity differentially correlated with sucrose preference and passivity measures. CONCLUSIONS: These data demonstrate that the rVTA and cVTA respond differently to stress and suggest that while cVTA activity may be related to passivity-like states, the activity of both subregions appears to be related to anhedonia and the processing of incentive value. These region-dependent abnormalities indicate the multi-modular composition of the VTA, which could provide multiple substrates for different symptom features.
Authors: Mina G Nashed; Shannon Waye; S M Nageeb Hasan; Diana Nguyen; Micaela Wiseman; Jing Zhang; Harry Lau; O Chandani Dinesh; Roger Raymond; Iain R Greig; Francis Rodriguez Bambico; José N Nobrega Journal: Psychopharmacology (Berl) Date: 2022-01-04 Impact factor: 4.530
Authors: Luis A Trujillo-Villarreal; Viktor J Romero-Díaz; Iván Alberto Marino-Martínez; Lizeth Fuentes-Mera; Marco Antonio Ponce-Camacho; Gabriel A Devenyi; M Mallar Chakravarty; Alberto Camacho-Morales; Eduardo E Garza-Villarreal Journal: Transl Psychiatry Date: 2021-01-14 Impact factor: 6.222