PMID- 34405459
OWN - NLM
STAT- MEDLINE
DCOM- 20210924
LR  - 20210924
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Linking)
VI  - 54
IP  - 6
DP  - 2021 Sep
TI  - Rapamycin prevents the long-term impairing effects of adolescence 
      Delta-9-tetrahydrocannabinol on memory and plasticity in male rats.
PG  - 6104-6122
LID - 10.1111/ejn.15425 [doi]
AB  - Long-lasting cognitive impairment is one of the most central negative 
      consequences related to the exposure to cannabis during adolescence and 
      particularly of Delta-9-tetrahydrocannabinol (THC). The aim of this study was to 
      compare the protracted effects of adolescent versus late-adolescent chronic 
      exposure to THC on short-term memory and plasticity and to examine whether 
      rapamycin, a blocker of the mammalian target of rapamycin (mTOR) pathway, can 
      restore THC-induced deficits in memory and plasticity. Male rats were injected 
      with ascending doses of THC [2.5, 5, 10 mg/kg; intraperitoneally (i.p.)] during 
      adolescence and late-adolescence (post-natal days 30-41 and 45-56, respectively), 
      followed by daily injections of rapamycin (1 mg/kg, i.p.) during the first 
      10 days of cessation from THC. Thirty days after the last injection, rats were 
      tested for short-term and working memory, anxiety-like behaviour, and plasticity 
      in the pathways projecting from the ventral subiculum (vSub) of the hippocampus 
      to the prefrontal cortex (PFC) and nucleus accumbens (NAc). THC exposure in 
      adolescence, but not late-adolescence, was found to induce long-term deficits in 
      object recognition short-term memory and synaptic plasticity in the 
      hippocampal-accumbens pathway. Importantly, rapamycin rescued these persistent 
      effects of THC administered during adolescence. Our findings show that some forms 
      of memory and plasticity are sensitive to chronic THC administration during 
      adolescence and that rapamycin administered during THC cessation may restore 
      cognitive function and plasticity, thus potentially protecting against the 
      possible long-term harmful effects of THC.
CI  - (c) 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Sabran-Cohen, Talia
AU  - Sabran-Cohen T
AD  - Department of Psychology, School of Psychological Sciences, University of Haifa, 
      Haifa, Israel.
AD  - The Integrated Brain and Behavior Research Center, University of Haifa, Haifa, 
      Israel.
FAU - Bright, Uri
AU  - Bright U
AD  - Department of Psychology, School of Psychological Sciences, University of Haifa, 
      Haifa, Israel.
AD  - The Integrated Brain and Behavior Research Center, University of Haifa, Haifa, 
      Israel.
FAU - Mizrachi Zer-Aviv, Tomer
AU  - Mizrachi Zer-Aviv T
AD  - Department of Psychology, School of Psychological Sciences, University of Haifa, 
      Haifa, Israel.
AD  - The Integrated Brain and Behavior Research Center, University of Haifa, Haifa, 
      Israel.
FAU - Akirav, Irit
AU  - Akirav I
AUID- ORCID: 0000-0002-7633-5953
AD  - Department of Psychology, School of Psychological Sciences, University of Haifa, 
      Haifa, Israel.
AD  - The Integrated Brain and Behavior Research Center, University of Haifa, Haifa, 
      Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210908
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Hallucinogens)
RN  - 7J8897W37S (Dronabinol)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - *Dronabinol/pharmacology
MH  - *Hallucinogens
MH  - Hippocampus
MH  - Male
MH  - Prefrontal Cortex
MH  - Rats
MH  - Sirolimus/pharmacology
OTO - NOTNLM
OT  - LTP
OT  - adolescence
OT  - cannabis
OT  - nucleus accumbens
OT  - short-term memory
EDAT- 2021/08/19 06:00
MHDA- 2021/09/25 06:00
CRDT- 2021/08/18 06:45
PHST- 2021/07/01 00:00 [revised]
PHST- 2021/02/16 00:00 [received]
PHST- 2021/08/09 00:00 [accepted]
PHST- 2021/08/19 06:00 [pubmed]
PHST- 2021/09/25 06:00 [medline]
PHST- 2021/08/18 06:45 [entrez]
AID - 10.1111/ejn.15425 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2021 Sep;54(6):6104-6122. doi: 10.1111/ejn.15425. Epub 2021 Sep 
      8.