PMID- 29596901
OWN - NLM
STAT- MEDLINE
DCOM- 20190220
LR  - 20191210
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 135
DP  - 2018 Jun
TI  - Periaqueductal gray glutamatergic, cannabinoid and vanilloid receptor interplay 
      in defensive behavior and aversive memory formation.
PG  - 399-411
LID - S0028-3908(18)30144-8 [pii]
LID - 10.1016/j.neuropharm.2018.03.032 [doi]
AB  - Stimulation of the midbrain periaqueductal gray matter (PAG) in humans elicits 
      sensations of fear and impending terror, and mediates predator defensive 
      responses in rodents. In rats, pharmacological stimulation of the dorsolateral 
      portion of the PAG (dlPAG) with N-Methyl-d-Aspartate (NMDA) induces aversive 
      conditioning that acts as an unconditioned stimulus (US). In the present work, we 
      investigated the interplay between the vanilloid TRPV1 and cannabinoid CB1 
      receptors in the NMDA-dlPAG defensive response and in subsequent aversive 
      learning. Rats were subjected to dlPAG NMDA infusion in an olfactory conditioned 
      stimulus (CS) task allowing the evaluation of immediate and long-term defensive 
      behavioral responses during CS presentation. The results indicated that an 
      intermediate dose of NMDA (50 pmol) induced both immediate and long-term effects. 
      A sub-effective dose of NMDA (25 pmol) was potentiated by the TRPV1 receptor 
      agonist capsaicin (CAP, 1 nmol) and the CB1 receptor antagonist, AM251 
      (200 pmol). CAP (10 nmol) or the combination of CAP (1 nmol) and AM251 (200 pmol) 
      induced long-term effects without increasing immediate defensive responses. The 
      glutamate release inhibitor riluzole (2 or 4 nmol) and the AMPA/kainate receptor 
      antagonist DNQX (2 or 4 nmol) potentiated the immediate effects but blocked the 
      long-term effects. The results showed that immediate defensive responses rely on 
      NMDA receptors, and aversive learning on the fine-tuning of TRPV1, CB1, 
      metabotropic glutamate and AMPA receptors located in pre- and postsynaptic 
      membranes. In conclusion, the activity of the dlPAG determines core affective 
      aspects of aversive memory formation controlled by local TRPV1/CB1 balance.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Back, Franklin P
AU  - Back FP
AD  - Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, 
      Florianopolis, SC, 88049-900, Brazil.
FAU - Carobrez, Antonio P
AU  - Carobrez AP
AD  - Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, 
      Florianopolis, SC, 88049-900, Brazil. Electronic address: padua.carobrez@ufsc.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180326
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Receptors, Cannabinoid)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (TRPV Cation Channels)
SB  - IM
MH  - Animals
MH  - Avoidance Learning/drug effects/*physiology
MH  - Behavior, Animal/drug effects/physiology
MH  - Conditioning, Psychological/drug effects/physiology
MH  - Male
MH  - Memory/drug effects/*physiology
MH  - Neurotransmitter Agents/pharmacology
MH  - Olfactory Perception/drug effects/physiology
MH  - Periaqueductal Gray/drug effects/*metabolism
MH  - Random Allocation
MH  - Rats, Wistar
MH  - Receptors, Cannabinoid/*metabolism
MH  - Receptors, Glutamate/*metabolism
MH  - TRPV Cation Channels/*metabolism
OTO - NOTNLM
OT  - AMPA receptors
OT  - Aversive memory formation
OT  - CB1 receptors
OT  - NMDA receptors
OT  - Olfactory fear conditioning
OT  - TRPV1 receptors
EDAT- 2018/03/30 06:00
MHDA- 2019/03/21 06:00
CRDT- 2018/03/30 06:00
PHST- 2017/10/25 00:00 [received]
PHST- 2018/03/07 00:00 [revised]
PHST- 2018/03/23 00:00 [accepted]
PHST- 2018/03/30 06:00 [pubmed]
PHST- 2019/03/21 06:00 [medline]
PHST- 2018/03/30 06:00 [entrez]
AID - S0028-3908(18)30144-8 [pii]
AID - 10.1016/j.neuropharm.2018.03.032 [doi]
PST - ppublish
SO  - Neuropharmacology. 2018 Jun;135:399-411. doi: 10.1016/j.neuropharm.2018.03.032. 
      Epub 2018 Mar 26.