PMID- 15970947
OWN - NLM
STAT- MEDLINE
DCOM- 20060512
LR  - 20181201
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 31
IP  - 3
DP  - 2006 Mar
TI  - Differential effects of two chronic diazepam treatment regimes on withdrawal 
      anxiety and AMPA receptor characteristics.
PG  - 602-19
AB  - Withdrawal from chronic benzodiazepines is associated with increased anxiety and 
      seizure susceptibility. Neuroadaptive changes in neural activity occur in 
      limbo-cortical structures although changes at the level of the GABA(A) receptor 
      do not provide an adequate explanation for these functional changes. We have 
      employed two diazepam treatment regimes known to produce differing effects on 
      withdrawal aversion in the rat and examined whether withdrawal-induced anxiety 
      was accompanied by changes in AMPA receptor characteristics. Rats were given 28 
      days treatment with diazepam by the intraperitoneal (i.p.) route (5 mg/kg) and 
      the subcutaneous (s.c.) route (15 mg/kg). Withdrawal anxiety in the elevated plus 
      maze was evident in the group withdrawn from chronic s.c. diazepam (relatively 
      more stable plasma levels) but not from the chronic i.p. group (fluctuating daily 
      plasma levels). In the brains of these rats, withdrawal anxiety was accompanied 
      by increased [3H]Ro48 8587 binding in the hippocampus and thalamus, and decreased 
      GluR1 and GluR2 subunit mRNA expression in the amygdala (GluR1 and GluR2) and 
      cortex (GluR1). The pattern of changes was different in the chronic i.p. group 
      where in contrast to the chronic s.c. group, there was reduced [3H]Ro48 8587 
      binding in the hippocampus and no alterations in GluR1 and GluR2 subunit 
      expression in the amygdala. While both groups showed reduced GluR1 mRNA subunit 
      expression in the cortex overall, only the agranular insular cortex exhibited 
      marked reductions following chronic i.p. diazepam. Striatal GluR2 mRNA expression 
      was increased in the i.p. group but not the s.c. group. Taken together, these 
      data are consistent with differential neuroadaptive processes in AMPA receptor 
      plasticity being important in withdrawal from chronic benzodiazepines. Moreover, 
      these processes may differ both at a regional and receptor function level 
      according to the behavioral manifestations of withdrawal.
FAU - Allison, Claire
AU  - Allison C
AD  - Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical 
      Sciences, University of Strathclyde, Glasgow, UK. claire.allison@strath.ac.uk
FAU - Pratt, Judith A
AU  - Pratt JA
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Imidazoles)
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (Quinazolines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Ro 48-8587)
RN  - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2)
RN  - Q3JTX2Q7TU (Diazepam)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
SB  - IM
MH  - Animals
MH  - Anxiety/etiology/*psychology
MH  - Autoradiography
MH  - Diazepam/*administration & dosage/*adverse effects
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Hypnotics and Sedatives/*administration & dosage/*adverse effects
MH  - Imidazoles/pharmacology
MH  - In Situ Hybridization
MH  - Injections, Intraperitoneal
MH  - Injections, Subcutaneous
MH  - Male
MH  - Oligonucleotide Probes
MH  - Quinazolines/pharmacology
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Rats
MH  - Rats, Long-Evans
MH  - Receptors, AMPA/*drug effects/genetics
MH  - Substance Withdrawal Syndrome/etiology/*psychology
EDAT- 2005/06/23 09:00
MHDA- 2006/05/13 09:00
CRDT- 2005/06/23 09:00
PHST- 2005/06/23 09:00 [pubmed]
PHST- 2006/05/13 09:00 [medline]
PHST- 2005/06/23 09:00 [entrez]
AID - 1300800 [pii]
AID - 10.1038/sj.npp.1300800 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2006 Mar;31(3):602-19. doi: 10.1038/sj.npp.1300800.