PMID- 37442333
OWN - NLM
STAT- MEDLINE
DCOM- 20230907
LR  - 20230929
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 127
DP  - 2023 Dec 20
TI  - Recency memory is altered in cocaine-withdrawn adolescent rats: Implication of 
      cortical mTOR signaling.
PG  - 110822
LID - S0278-5846(23)00108-2 [pii]
LID - 10.1016/j.pnpbp.2023.110822 [doi]
AB  - In humans, cocaine abuse during adolescence poses a significant risk for 
      developing cognitive deficits later in life. Among the regions responsible for 
      cognitive processes, the medial prefrontal cortex (mPFC) modulates temporal order 
      information via mechanisms involving the mammalian-target of rapamycin 
      (mTOR)-mediated pathway and protein synthesis regulation. Accordingly, our goal 
      was to study the effect of repeated cocaine exposure during both adolescence and 
      adulthood on temporal memory by studying the mTOR pathway in the mPFC. Adolescent 
      or adult rats underwent repeated cocaine injections for 15 days and, after two 
      weeks of withdrawal, engaged in the temporal order object recognition (TOOR) 
      test. We found that repeated cocaine exposure during adolescence impaired TOOR 
      performance, while control or adult-treated animals showed no impairments. 
      Moreover, activation of the mTOR-S6-eEF2 pathway following the TOOR test was 
      diminished only in the adolescent cocaine-treated group. Notably, inhibition of 
      the mTOR-mediated pathway by rapamycin injection impaired TOOR performance in 
      naive adolescent and adult animals, revealing this pathway to be a critical 
      component in regulating recency memory. Our data indicate that withdrawal from 
      cocaine exposure impairs recency memory via the dysregulation of protein 
      translation mechanisms, but only when cocaine is administered during adolescence.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Castillo Diaz, Fernando
AU  - Castillo Diaz F
AD  - Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', 
      Universita degli Studi di Milano, Milan 20133, Italy; Department of Behavioural 
      and Molecular Neurobiology, University of Regensburg, Regensburg 93053, Germany.
FAU - Mottarlini, Francesca
AU  - Mottarlini F
AD  - Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', 
      Universita degli Studi di Milano, Milan 20133, Italy.
FAU - Targa, Giorgia
AU  - Targa G
AD  - Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', 
      Universita degli Studi di Milano, Milan 20133, Italy.
FAU - Rizzi, Beatrice
AU  - Rizzi B
AD  - Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', 
      Universita degli Studi di Milano, Milan 20133, Italy; Center for Neuroscience, 
      University of Camerino, Camerino 62032, Italy.
FAU - Fumagalli, Fabio
AU  - Fumagalli F
AD  - Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', 
      Universita degli Studi di Milano, Milan 20133, Italy. Electronic address: 
      fabio.fumagalli@unimi.it.
FAU - Caffino, Lucia
AU  - Caffino L
AD  - Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', 
      Universita degli Studi di Milano, Milan 20133, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230711
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - I5Y540LHVR (Cocaine)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Animals
MH  - Adolescent
MH  - *Cocaine/pharmacology
MH  - Sirolimus/pharmacology
MH  - Memory
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Prefrontal Cortex/metabolism
MH  - Mammals/metabolism
OTO - NOTNLM
OT  - Adolescence
OT  - Cocaine
OT  - Prefrontal cortex
OT  - Rapamycin
OT  - Temporal order memory
OT  - mTOR
COIS- Declaration of Competing Interest The authors of the manuscript certify that they 
      have NO affiliations with or involvement in any organization or entity with any 
      financial interest (such as honoraria; educational grants; participation in 
      speakers' bureaus; membership, employment, consultancies, stock ownership, or 
      other equity interest; and expert testimony or patent-licensing arrangements), or 
      non-financial interest (such as personal or professional relationships, 
      affiliations, knowledge or beliefs) in the subject matter or materials discussed 
      in this manuscript.
EDAT- 2023/07/14 13:07
MHDA- 2023/09/07 06:42
CRDT- 2023/07/13 19:25
PHST- 2022/12/12 00:00 [received]
PHST- 2023/06/28 00:00 [revised]
PHST- 2023/07/06 00:00 [accepted]
PHST- 2023/09/07 06:42 [medline]
PHST- 2023/07/14 13:07 [pubmed]
PHST- 2023/07/13 19:25 [entrez]
AID - S0278-5846(23)00108-2 [pii]
AID - 10.1016/j.pnpbp.2023.110822 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2023 Dec 20;127:110822. doi: 
      10.1016/j.pnpbp.2023.110822. Epub 2023 Jul 11.