Regulation of benzodiazepine receptor binding and GABA subunit
نویسندگان
چکیده
Quantitative autoradiography of benzodiazepine (BZ) receptors and competitive reverse transcription–polymerase chain reaction were used to characterize changes in BZ binding and GABA receptor subunit transcription levels associated with the anxiolytic effects of A alprazolam. Effects were assessed on punished and non-suppressed water consumption using a lick suppression (Vogel) paradigm. 3 Alprazolam had no effect on non-suppressed licking, [ H]Ro 15-1788 binding or receptor subunit transcript levels, compared to non-drug controls. When each fifth lick produced a shock (0–0.5 mA), responding was suppressed in an intensity-related manner. The highest 3 intensity significantly decreased licking (85%), [ H]Ro 15-1788 binding (12%) and a1 transcript levels (63%) in the basolateral nucleus 3 of the amygdala, and [ H]Ro 15-1788 binding in the mediodorsal thalamic nucleus (15%), compared to non-punished controls. Punishment increased the ratio of g2L/S transcripts in the basolateral nucleus of the amygdala. Alprazolam blocked or reversed each of these effects. These results show that punishment has similar effects on BZ binding and GABA receptor subunit expression and that A alprazolam can block or reverse those effects. Such changes may be related to the anxiolytic effects of alprazolam. 2000 Elsevier Science B.V. All rights reserved. Theme: Neural basis of behavior Topic: Motivation and emotion
منابع مشابه
Structural determinants of benzodiazepine allosteric regulation of GABA(A) receptor currents.
Benzodiazepine enhancement of GABA(A) receptor current requires a gamma subunit, and replacement of the gamma subunit by the delta subunit abolishes benzodiazepine enhancement. Although it has been demonstrated that benzodiazepines bind to GABA(A) receptors at the junction between alpha and gamma subunits, the structural basis for the coupling of benzodiazepine binding to allosteric enhancement...
متن کاملDown-Regulation of Benzodiazepine Binding to a5 Subunit- Containing g-Aminobutyric AcidA Receptors in Tolerant Rat Brain Indicates Particular Involvement of the Hippocampal CA1 Region
Chronic benzodiazepine treatment can produce tolerance and changes in g-aminobutyric acid (GABA)A receptors. To study the effect of treatment on a selected population of receptors, assays were performed using [H]RY-80, which is selective for GABAA receptors with an a5 subunit. Rats were given a flurazepam treatment known to produce tolerance and down-regulation of benzodiazepine binding, or a d...
متن کاملDown-regulation of benzodiazepine binding to alpha 5 subunit-containing gamma-aminobutyric Acid(A) receptors in tolerant rat brain indicates particular involvement of the hippocampal CA1 region.
Chronic benzodiazepine treatment can produce tolerance and changes in gamma-aminobutyric acid (GABA)(A) receptors. To study the effect of treatment on a selected population of receptors, assays were performed using [(3)H]RY-80, which is selective for GABA(A) receptors with an alpha 5 subunit. Rats were given a flurazepam treatment known to produce tolerance and down-regulation of benzodiazepine...
متن کاملAcute pentylenetetrazol injection reduces rat GABAA receptor mRNA levels and GABA stimulation of benzodiazepine binding with No effect on benzodiazepine binding site density.
The effects of a single convulsive dose of pentylenetetrazol (PTZ, 45 mg/kg i.p.) on rat brain gamma-aminobutyric acid type A (GABAA) receptors were studied. Selected GABAA receptor subunit mRNAs were measured by Northern blot analysis (with beta-actin mRNA as a standard). Four hours after PTZ, the GABAA receptor gamma2-mRNA was decreased in hippocampus, cerebral cortex, and cerebellum; alpha1-...
متن کاملBenzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes.
GABA(A) (gamma-aminobutyric acid(A)) receptors are molecular substrates for the regulation of vigilance, anxiety, muscle tension, epileptogenic activity and memory functions, which is evident from the spectrum of actions elicited by clinically effective drugs acting at their modulatory benzodiazepine-binding site. Here we show, by introducing a histidine-to-arginine point mutation at position 1...
متن کامل