PMID- 34483875
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210907
IS  - 1663-3563 (Print)
IS  - 1663-3563 (Electronic)
IS  - 1663-3563 (Linking)
VI  - 13
DP  - 2021
TI  - Endocannabinoids Released in the Ventral Tegmental Area During Copulation to 
      Satiety Modulate Changes in Glutamate Receptors Associated With Synaptic 
      Plasticity Processes.
PG  - 701290
LID - 10.3389/fnsyn.2021.701290 [doi]
LID - 701290
AB  - Endocannabinoids modulate mesolimbic (MSL) dopamine (DA) neurons firing at the 
      ventral tegmental area (VTA). These neurons are activated by copulation, 
      increasing DA release in nucleus accumbens (NAcc). Copulation to satiety in male 
      rats implies repeated ejaculation within a short period (around 2.5 h), during 
      which NAcc dopamine concentrations remain elevated, suggesting continuous 
      neuronal activation. During the 72 h that follow copulation to satiety, males 
      exhibit long-lasting changes suggestive of brain plasticity processes. Enhanced 
      DA neuron activity triggers the synthesis and release of endocannabinoids (eCBs) 
      in the VTA, which participate in several long-term synaptic plasticity processes. 
      Blockade of cannabinoid type 1 receptors (CB1Rs) during copulation to satiety 
      interferes with the appearance of the plastic changes. Glutamatergic inputs to 
      the VTA express CB1Rs and contribute to DA neuron burst firing and synaptic 
      plasticity. We hypothesized that eCBs, released during copulation to satiety, 
      would activate VTA CB1Rs and modulate synaptic plasticity processes involving 
      glutamatergic transmission. To test this hypothesis, we determined changes in VTA 
      CB1R density, phosphorylation, and internalization in rats that copulated to 
      satiety 24 h earlier as compared both to animals that ejaculated only once and to 
      sexually experienced unmated males. Changes in glutamate AMPAR and NMDAR 
      densities and subunit composition and in ERK1/2 activation were determined in the 
      VTA of males that copulated to satiety in the presence or absence of AM251, a 
      CB1R antagonist. The CB1R density decreased and the proportion of phosphorylated 
      CB1Rs increased in the animals that copulated compared to control rats. The CB1R 
      internalization was detected only in sexually satiated males. A decrease in 
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) density, 
      blocked by AM251 pretreatment, and an increase in the proportion of GluA2-AMPARs 
      occurred in sexually satiated rats. GluN2A- N-methyl-D-aspartate receptor (NMDAR) 
      expression decreased, and GluN2B-NMDARs increased in these animals, both of which 
      were prevented by AM251 pre-treatment. An increase in phosphorylated ERK1/2 
      emerged in males copulating to satiety in the presence of AM251. Results 
      demonstrate that during copulation to satiety, eCBs activate CB1Rs in the VTA, 
      producing changes in glutamate receptors compatible with a reduced neuronal 
      activation. These changes could play a role in the induction of the long-lasting 
      physiological changes that characterize sexually satiated rats.
CI  - Copyright (c) 2021 Rodriguez-Manzo, Gonzalez-Morales and Garduno-Gutierrez.
FAU - Rodriguez-Manzo, Gabriela
AU  - Rodriguez-Manzo G
AD  - Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados 
      (Cinvestav-Sede Sur), Ciudad de Mexico, Mexico.
FAU - Gonzalez-Morales, Estefania
AU  - Gonzalez-Morales E
AD  - Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados 
      (Cinvestav-Sede Sur), Ciudad de Mexico, Mexico.
FAU - Garduno-Gutierrez, Rene
AU  - Garduno-Gutierrez R
AD  - Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados 
      (Cinvestav-Sede Sur), Ciudad de Mexico, Mexico.
LA  - eng
PT  - Journal Article
DEP - 20210818
PL  - Switzerland
TA  - Front Synaptic Neurosci
JT  - Frontiers in synaptic neuroscience
JID - 101548972
PMC - PMC8416467
OTO - NOTNLM
OT  - AMPA and NMDA glutamate receptors
OT  - CB1 receptors
OT  - endocannabinoids
OT  - mesolimbic circuit
OT  - natural reward
OT  - sexual satiety
OT  - synaptic plasticity
OT  - ventral tegmental area
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/09/07 06:00
MHDA- 2021/09/07 06:01
PMCR- 2021/01/01
CRDT- 2021/09/06 05:54
PHST- 2021/04/27 00:00 [received]
PHST- 2021/07/08 00:00 [accepted]
PHST- 2021/09/06 05:54 [entrez]
PHST- 2021/09/07 06:00 [pubmed]
PHST- 2021/09/07 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fnsyn.2021.701290 [doi]
PST - epublish
SO  - Front Synaptic Neurosci. 2021 Aug 18;13:701290. doi: 10.3389/fnsyn.2021.701290. 
      eCollection 2021.