PMID- 20730418
OWN - NLM
STAT- MEDLINE
DCOM- 20110225
LR  - 20211020
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 212
IP  - 4
DP  - 2010 Dec
TI  - Residual social, memory and oxytocin-related changes in rats following repeated 
      exposure to gamma-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or 
      their combination.
PG  - 663-74
LID - 10.1007/s00213-010-1986-5 [doi]
AB  - RATIONALE: There has been little investigation of the possible lasting adverse 
      effects of gamma-hydroxybutyrate (GHB). OBJECTIVES: This study aims to study whether 
      GHB produces residual adverse effects on memory and social behaviour in rats and 
      lasting changes in brain monoamines and oxytocin-related gene expression. 
      METHODS: Rats received daily intraperitoneal injections of GHB (500 mg/kg), 
      methylenedioxymethamphetamine (MDMA; 5 mg/kg) or their combination (GHB/MDMA) 
      over ten consecutive days. Locomotor activity and body weight were assessed 
      during the dosing period and withdrawal-related anxiety was assessed 24 h after 
      drug cessation. After a washout of 4 weeks, rats were tested on the emergence, 
      social interaction, and object recognition tasks over a 2-week period. Monoamine 
      levels in cortex and striatum, and hypothalamic oxytocin and oxytocin receptor 
      mRNA, were then assessed. RESULTS: MDMA and GHB/MDMA caused modest sensitization 
      of locomotor activity over time, while sedative effects of GHB diminished with 
      repeated exposure. GHB-treated rats showed reduced social interaction 24 h after 
      the final dose, indicating GHB withdrawal-induced anxiety. All drug-treated 
      groups displayed residual deficits in social interaction and object recognition. 
      No changes in monoamine levels were detected 8 weeks post-drug. However, MDMA 
      pre-exposure increased hypothalamic oxytocin mRNA while GHB pre-exposure 
      upregulated oxytocin receptor mRNA. GHB/MDMA pre-exposure caused intermediate 
      changes in both of these measures. CONCLUSIONS: GHB treatment caused residual 
      impairments in memory and social behaviour and increases in anxiety, paralleling 
      the lasting adverse effects of MDMA. Both drugs caused lasting neuroadaptations 
      in brain oxytocin systems and this may be related to the long-term social 
      interaction deficiencies caused by both drugs.
FAU - van Nieuwenhuijzen, Petra S
AU  - van Nieuwenhuijzen PS
AD  - School of Psychology, University of Sydney, Sydney, NSW, 2006, Australia. 
      petra.s.van@gmail.com
FAU - Long, Leonora E
AU  - Long LE
FAU - Hunt, Glenn E
AU  - Hunt GE
FAU - Arnold, Jonathon C
AU  - Arnold JC
FAU - McGregor, Iain S
AU  - McGregor IS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100821
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Biogenic Monoamines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Oxytocin)
RN  - 50-56-6 (Oxytocin)
RN  - 7G33012534 (Sodium Oxybate)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Anxiety/chemically induced/metabolism/psychology
MH  - Behavior, Animal/*drug effects
MH  - Biogenic Monoamines/metabolism
MH  - Body Weight/drug effects
MH  - Brain/*drug effects/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Emotions/drug effects
MH  - Gene Expression Regulation
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Memory/*drug effects
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & 
      dosage/*pharmacology/toxicity
MH  - Oxytocin/genetics/*metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Oxytocin/genetics/metabolism
MH  - Recognition, Psychology/drug effects
MH  - *Social Behavior
MH  - Sodium Oxybate/administration & dosage/*pharmacology/toxicity
MH  - Substance Withdrawal Syndrome/etiology/metabolism/psychology
MH  - Time Factors
EDAT- 2010/08/24 06:00
MHDA- 2011/02/26 06:00
CRDT- 2010/08/24 06:00
PHST- 2010/02/05 00:00 [received]
PHST- 2010/08/06 00:00 [accepted]
PHST- 2010/08/24 06:00 [entrez]
PHST- 2010/08/24 06:00 [pubmed]
PHST- 2011/02/26 06:00 [medline]
AID - 10.1007/s00213-010-1986-5 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2010 Dec;212(4):663-74. doi: 
      10.1007/s00213-010-1986-5. Epub 2010 Aug 21.