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Differential effects of two chronic diazepam treatment regimes on withdrawal anxiety and AMPA receptor characteristics.
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2006 Mar; Vol. 31 (3), pp. 602-19. - Publication Year :
- 2006
-
Abstract
- 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 Withdrawal anxiety in the elevated plus maze was evident in the group withdrawn from chronic s.c. diazepam (relatively more stable plasma levels) but not from the chronic i.p. group (fluctuating daily plasma levels).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.
- Subjects :
- Animals
Anxiety etiology
Autoradiography
Excitatory Amino Acid Antagonists pharmacology
Imidazoles pharmacology
In Situ Hybridization
Injections, Intraperitoneal
Injections, Subcutaneous
Male
Oligonucleotide Probes
Quinazolines pharmacology
RNA, Messenger biosynthesis
RNA, Messenger genetics
Rats
Rats, Long-Evans
Receptors, AMPA genetics
Substance Withdrawal Syndrome etiology
Anxiety psychology
Diazepam administration & dosage
Diazepam adverse effects
Hypnotics and Sedatives administration & dosage
Hypnotics and Sedatives adverse effects
Receptors, AMPA drug effects
Substance Withdrawal Syndrome psychology
Subjects
Details
- Language :
- English
- ISSN :
- 0893-133X
- Volume :
- 31
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15970947
- Full Text :
- https://doi.org/10.1038/sj.npp.1300800