PMID- 19446408
OWN - NLM
STAT- MEDLINE
DCOM- 20090825
LR  - 20191210
IS  - 1879-0046 (Electronic)
IS  - 0376-8716 (Linking)
VI  - 103
IP  - 3
DP  - 2009 Aug 1
TI  - Sedative and hypothermic effects of gamma-hydroxybutyrate (GHB) in rats alone and 
      in combination with other drugs: assessment using biotelemetry.
PG  - 137-47
LID - 10.1016/j.drugalcdep.2009.03.004 [doi]
AB  - The recreational drug gamma-hydroxybutyrate (GHB) has euphoric effects and can 
      induce sedation and body temperature changes. GHB is frequently combined with 
      other recreational drugs although these interactions are not well characterised. 
      The present study used biotelemetry to provide a fine-grained analysis of the 
      effects of GHB on body temperature and locomotor activity in freely moving rats, 
      and investigated interactions between GHB and 3,4-methylenedioxymethamphetamine 
      (MDMA), methamphetamine (METH) and various antagonist drugs. GHB (1000mg/kg) 
      caused profound sedation for more than 2h and a complex triphasic effect on body 
      temperature: an initial hypothermia (5-40min), followed by hyperthermia 
      (40-140min), followed again by hypothermia (140-360min). A lower GHB dose 
      (500mg/kg) also caused sedation but only a hypothermic effect that lasted up to 
      6h. The dopamine D(1) receptor antagonist SCH 23390 (1mg/kg), the opioid 
      antagonist naltrexone (1mg/kg), the benzodiazepine antagonist flumazenil 
      (10mg/kg), and the 5-HT(2A/2C) receptor antagonist ritanserin (1mg/kg) did not 
      prevent the overall sedative or body temperature effects of GHB (1000mg/kg). 
      However the GABA(B) antagonist SCH 50911 (50mg/kg) prevented the hyperthermia 
      induced by GHB (1000mg/kg). Repeated daily administration of GHB (1000mg/kg) 
      produced tolerance to the sedative and hyperthermic effects of the drug and 
      cross-tolerance to the sedative effects of the GABA(B) receptor agonist baclofen 
      (10mg/kg). A high ambient temperature of 28 degrees C prevented the hypothermia 
      obtained with GHB (500mg/kg) at 20 degrees C, while GHB (500mg/kg) reduced the 
      hyperthermia and hyperactivity produced by co-administered doses of MDMA (5mg/kg) 
      or METH (1mg/kg) at 28 degrees C. These results further confirm a role for 
      GABA(B) receptors in the hypothermic and sedative effects of GHB and show an 
      interaction between GHB and MDMA, and GHB and METH, that may be relevant to the 
      experience of recreational users who mix these drugs.
FAU - van Nieuwenhuijzen, Petra S
AU  - van Nieuwenhuijzen PS
AD  - School of Psychology, University of Sydney, NSW, Australia.
FAU - McGregor, Iain S
AU  - McGregor IS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090514
PL  - Ireland
TA  - Drug Alcohol Depend
JT  - Drug and alcohol dependence
JID - 7513587
RN  - 0 ((+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid)
RN  - 0 (Benzazepines)
RN  - 0 (Illicit Drugs)
RN  - 0 (Morpholines)
RN  - 0 (SCH 23390)
RN  - 145TFV465S (Ritanserin)
RN  - 40P7XK9392 (Flumazenil)
RN  - 44RAL3456C (Methamphetamine)
RN  - 5S6W795CQM (Naltrexone)
RN  - 7G33012534 (Sodium Oxybate)
RN  - H789N3FKE8 (Baclofen)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Baclofen/pharmacology
MH  - Benzazepines/administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Drug Tolerance
MH  - Flumazenil/administration & dosage
MH  - Hypothermia/*chemically induced
MH  - Illicit Drugs/*pharmacology
MH  - Male
MH  - Methamphetamine/administration & dosage/pharmacology
MH  - Morpholines/administration & dosage
MH  - Motor Activity/*drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/pharmacology
MH  - Naltrexone/administration & dosage
MH  - Rats
MH  - Rats, Wistar
MH  - Ritanserin/administration & dosage
MH  - Sodium Oxybate/*administration & dosage/*pharmacology
MH  - *Telemetry
EDAT- 2009/05/19 09:00
MHDA- 2009/08/26 09:00
CRDT- 2009/05/19 09:00
PHST- 2008/11/06 00:00 [received]
PHST- 2009/01/22 00:00 [revised]
PHST- 2009/03/05 00:00 [accepted]
PHST- 2009/05/19 09:00 [entrez]
PHST- 2009/05/19 09:00 [pubmed]
PHST- 2009/08/26 09:00 [medline]
AID - S0376-8716(09)00083-0 [pii]
AID - 10.1016/j.drugalcdep.2009.03.004 [doi]
PST - ppublish
SO  - Drug Alcohol Depend. 2009 Aug 1;103(3):137-47. doi: 
      10.1016/j.drugalcdep.2009.03.004. Epub 2009 May 14.