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AMPA receptor autoradiography in mouse brain following single and repeated withdrawal from diazepam

Allison, C. and Pratt, J.A. and Ripley, T. and Stephens, D.N. (2005) AMPA receptor autoradiography in mouse brain following single and repeated withdrawal from diazepam. European Journal of Neuroscience, 21. pp. 1045-1056. ISSN 0953-816X

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Abstract

Withdrawal from chronic treatment with benzodiazepines is associated with increased neuronal excitability leading to anxiety, aversive effects and increased seizure sensitivity. After repeated withdrawal experiences, seizure sensitivity increases while withdrawal-induced anxiety and aversion decrease. We used autoradiographical methods employing [(3)H]Ro48 8587, a selective ligand for glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, to study withdrawal-induced changes in AMPA receptor binding in areas of the mouse brain postulated to be involved in these responses. Mice were given 21 days treatment with diazepam (15 mg/kg, s.c. in sesame oil) followed by withdrawal (single withdrawal) or three blocks of 7 days treatment interspersed with 3-day periods to allow washout of drug (repeated withdrawal). In keeping with heightened excitability in withdrawal from chronic diazepam treatment, the single withdrawal group showed, 72 h after their final dose of diazepam, increased [(3)H]Ro48 8587 binding in several brain areas associated with emotional responses or seizure activity, including hippocampal subfields, amygdalar and thalamic nuclei and motor cortex. In contrast, the repeated withdrawal group showed no changes in [(3)H]Ro48 8587 binding in any brain area studied. These observations are consistent with up-regulation of AMPA receptor-mediated transmission being important in withdrawal-induced anxiety and aversion but not in increased seizure sensitivity associated with repeated withdrawal. As changes in AMPA receptor subunit expression alter the functionality of the receptor, future studies will address this possibility.

Item type: Article
ID code: 10044
Keywords: amygdala, thalamus, plasticity, neuroadaptation, hippocampus, dependence, anxiety, Pharmacy and materia medica, Neuroscience(all)
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences > Physiology and Pharmacology
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 23 Jun 2011 11:00
    Last modified: 04 Sep 2014 19:39
    URI: http://strathprints.strath.ac.uk/id/eprint/10044

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