PMID- 22821081
OWN - NLM
STAT- MEDLINE
DCOM- 20130611
LR  - 20211021
IS  - 1432-1106 (Electronic)
IS  - 0014-4819 (Linking)
VI  - 221
IP  - 4
DP  - 2012 Sep
TI  - Long-term behavioral and biochemical effects of an ultra-low dose of 
      Delta9-tetrahydrocannabinol (THC): neuroprotection and ERK signaling.
PG  - 437-48
LID - 10.1007/s00221-012-3186-5 [doi]
AB  - We have previously reported that a single injection of an ultra-low dose of 
      delta-9-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) 
      protected the brain from pentylenentetrazole (PTZ)-induced cognitive deficits 
      when applied 1-7 days before or 1-3 days after the insult. In the present study 
      we expanded the protective profile of THC by showing that it protected mice from 
      cognitive deficits that were induced by a variety of other neuronal insults, 
      including pentobarbital-induced deep anesthesia, repeated treatment with 3,4 
      methylenedioxymethamphetamine (MDMA; "ecstasy") and exposure to carbon monoxide. 
      The protective effect of THC lasted for at least 7 weeks. The same ultra-low dose 
      of THC (0.002 mg/kg, a dose that is 3-4 orders of magnitude lower than the doses 
      that produce the known acute effects of the drug in mice) induced long-lasting 
      (7 weeks) modifications of extracellular signal-regulated kinase (ERK) activity 
      in the hippocampus, frontal cortex and cerebellum of the mice. The alterations in 
      ERK activity paralleled changes in its activating enzyme MEK and its inactivating 
      enzyme MKP-1. Furthermore, a single treatment with the low dose of THC elevated 
      the level of pCREB (phosphorylated cAMP response element-binding protein) in the 
      hippocampus and the level of BDNF (brain-derived neurotrophic factor) in the 
      frontal cortex. These long-lasting effects indicate that a single treatment with 
      an ultra-low dose of THC can modify brain plasticity and induce long-term 
      behavioral and developmental effects in the brain.
FAU - Fishbein, Miriam
AU  - Fishbein M
AD  - The Adelson Center for the Biology of Addictive Diseases and The Mauerberger 
      Chair in Neuropharmacology, Sackler Faculty of Medicine, Tel-Aviv University, 
      Tel-Aviv 69978, Israel.
FAU - Gov, Sahar
AU  - Gov S
FAU - Assaf, Fadi
AU  - Assaf F
FAU - Gafni, Mikhal
AU  - Gafni M
FAU - Keren, Ora
AU  - Keren O
FAU - Sarne, Yosef
AU  - Sarne Y
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120722
PL  - Germany
TA  - Exp Brain Res
JT  - Experimental brain research
JID - 0043312
RN  - 0 (Neuroprotective Agents)
RN  - 7J8897W37S (Dronabinol)
SB  - IM
MH  - Animals
MH  - Cognition Disorders/*drug therapy/*metabolism/prevention & control
MH  - Dronabinol/*pharmacology
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Neuronal Plasticity/drug effects/*physiology
MH  - Neuroprotective Agents/*pharmacology
EDAT- 2012/07/24 06:00
MHDA- 2013/06/12 06:00
CRDT- 2012/07/24 06:00
PHST- 2012/06/11 00:00 [received]
PHST- 2012/07/03 00:00 [accepted]
PHST- 2012/07/24 06:00 [entrez]
PHST- 2012/07/24 06:00 [pubmed]
PHST- 2013/06/12 06:00 [medline]
AID - 10.1007/s00221-012-3186-5 [doi]
PST - ppublish
SO  - Exp Brain Res. 2012 Sep;221(4):437-48. doi: 10.1007/s00221-012-3186-5. Epub 2012 
      Jul 22.