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Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity.
Neuroscience. 2013 Dec 03; 253:444-54.N

Abstract

Endocannabinoids (eCBs) are involved in the stress response and alterations in eCB signaling may contribute to the etiology of mood disorders. Exposure to chronic mild stress (CMS), a model of depression, produces downregulation of the cannabinoid 1 (CB1) receptor in the hippocampus of male rats. However, it is unknown how this stress-induced change in CB1 levels affects eCB-mediated neurotransmission. In vitro, field potential recordings from CMS-exposed (21-days) rats were performed to assess the effects of stress on eCB-regulated glutamatergic neurotransmission in/on hippocampal area CA1. We observed that application of the CB1 agonist, WIN 55,212-5 (1 μM), in stress animals resulted in a ∼135% increase in excitatory neurotransmission, whereas CB1 activation in non-stress animals leads to a ∼30% decrease. However, during blockade of GABA(A) neurotransmission with picrotoxin, CB1 activation yielded a ∼35% decrease in stress animals. These findings indicate that CMS does not directly affect glutamatergic neurotransmission. Rather, CMS sensitizes CB1 function on GABAergic terminals, leading to less inhibition and an increase in excitatory neurotransmission. This finding is reinforced in that induction of weak long-term-potentiation (LTP) is enhanced in CMS-exposed animals compared to controls and this enhancement is CB1-dependent. Lastly, we observed that the LTP-blocking property of WIN 55,212-5 shifts from being glutamate-dependent in non-stress animals to being GABA-dependent in stress animals. These results effectively demonstrate that CMS significantly alters hippocampal eCB-mediated neurotransmission and synaptic plasticity.

Authors+Show Affiliations

Program in Psychology, Ramapo College of New Jersey, Mahwah, NJ 07430, USA. Electronic address: creich@ramapo.edu.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24035826

Citation

Reich, C G., et al. "Adolescent Chronic Mild Stress Alters Hippocampal CB1 Receptor-mediated Excitatory Neurotransmission and Plasticity." Neuroscience, vol. 253, 2013, pp. 444-54.
Reich CG, Mihalik GR, Iskander AN, et al. Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity. Neuroscience. 2013;253:444-54.
Reich, C. G., Mihalik, G. R., Iskander, A. N., Seckler, J. C., & Weiss, M. S. (2013). Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity. Neuroscience, 253, 444-54. https://doi.org/10.1016/j.neuroscience.2013.08.066
Reich CG, et al. Adolescent Chronic Mild Stress Alters Hippocampal CB1 Receptor-mediated Excitatory Neurotransmission and Plasticity. Neuroscience. 2013 Dec 3;253:444-54. PubMed PMID: 24035826.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity. AU - Reich,C G, AU - Mihalik,G R, AU - Iskander,A N, AU - Seckler,J C, AU - Weiss,M S, Y1 - 2013/09/13/ PY - 2013/05/16/received PY - 2013/08/29/revised PY - 2013/08/29/accepted PY - 2013/9/17/entrez PY - 2013/9/17/pubmed PY - 2014/6/20/medline KW - 2-AG KW - 2-arachidonoyl-glycerol KW - ACSF KW - AEA KW - ANOVA KW - CB KW - CB1 receptor KW - CCK KW - CMS KW - CRS KW - DMSO KW - DSI KW - GC KW - HPA KW - LTP KW - MANOVAs KW - NS KW - PND KW - PTSD KW - PTX KW - S KW - TBS KW - analysis of variance KW - artificial cerebrospinal fluid KW - cannabinoid KW - cholecystokinin KW - chronic mild stress KW - chronic restraint stress KW - depolarization-induced-suppression of inhibition KW - depression KW - dimethyl sulfoxide KW - eCBs KW - endocannabinoid/endovanniloid anandamide KW - endocannabinoids KW - glucocorticoid KW - hippocampus KW - hypothalamic–pituitary–adrenal KW - long-term-potentiation KW - multivariate ANOVA KW - non-stress KW - picrotoxin KW - post natal day KW - post-traumatic-stress-disorder KW - stress KW - theta-burst stimulation SP - 444 EP - 54 JF - Neuroscience JO - Neuroscience VL - 253 N2 - Endocannabinoids (eCBs) are involved in the stress response and alterations in eCB signaling may contribute to the etiology of mood disorders. Exposure to chronic mild stress (CMS), a model of depression, produces downregulation of the cannabinoid 1 (CB1) receptor in the hippocampus of male rats. However, it is unknown how this stress-induced change in CB1 levels affects eCB-mediated neurotransmission. In vitro, field potential recordings from CMS-exposed (21-days) rats were performed to assess the effects of stress on eCB-regulated glutamatergic neurotransmission in/on hippocampal area CA1. We observed that application of the CB1 agonist, WIN 55,212-5 (1 μM), in stress animals resulted in a ∼135% increase in excitatory neurotransmission, whereas CB1 activation in non-stress animals leads to a ∼30% decrease. However, during blockade of GABA(A) neurotransmission with picrotoxin, CB1 activation yielded a ∼35% decrease in stress animals. These findings indicate that CMS does not directly affect glutamatergic neurotransmission. Rather, CMS sensitizes CB1 function on GABAergic terminals, leading to less inhibition and an increase in excitatory neurotransmission. This finding is reinforced in that induction of weak long-term-potentiation (LTP) is enhanced in CMS-exposed animals compared to controls and this enhancement is CB1-dependent. Lastly, we observed that the LTP-blocking property of WIN 55,212-5 shifts from being glutamate-dependent in non-stress animals to being GABA-dependent in stress animals. These results effectively demonstrate that CMS significantly alters hippocampal eCB-mediated neurotransmission and synaptic plasticity. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/24035826/Adolescent_chronic_mild_stress_alters_hippocampal_CB1_receptor_mediated_excitatory_neurotransmission_and_plasticity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00762-8 DB - PRIME DP - Unbound Medicine ER -