Influence of the Pituitary-Adrenal Axis on Benzodiazepine Receptor Binding to Rat Cerebral Cortex

Abstract

The role of the pituitary-adrenal axis on receptor binding and diurnal rhythmicity of benzodiazepines (BNZ) was assessed in the rat cerebral cortex. Groups of intact, adrenalectomized (ADx) and/or hypophysectomized (HPx) rats were killed at six different time intervals during the 24-hour cycle. BNZ binding was estimated by Scatchard analysis of ³H-flunitrazepam high-affinity binding to rat cerebral cortex. Intact and sham ADx animals show a similar pattern in diurnal thythm of BNZ binding, with a maximal concentration at midnight. Bilateral ADx induced a significant increase in B_max at all time intervals studied, the largest rise appearing at midnight. HPx alone led to a slightly smaller rise in B_max than in ADx rats, while HPx performed in ADx rats did not modify the response to ADx alone. B_maχ of BNZ binding in ADx rats reached maximal values at 3–7 days after surgery, and decreased somewhat at 15 days post-ADx. Corticosterone administration at a single dose of 5 mg i.p. 24 h before sacrifice returned B_max to normal values in ADx as well as in ADx plus HPx rats. The corticosterone effect is not exerted on the BNZ binding sites themselves, as revealed by the lack of effect of this glucocorticoid in vitro. These findings indicate that BNZ receptors in rat cerebral cortex can be modified by the adrenal gland, with corticosterone as a primary effector.

Mineralocorticoid and glucocorticoid receptors in the brain. Implications for ion permeability and transmitter systems

“…However, the latter may be secondary to a rise in ACTH levels after ADX (Kendall et al, 1982;DeSouza et al, 1986). In cortex, the binding characteristics were normalized with corticosterone treatment (Acuna et al, 1990).…”

“…Adrenalectomy generally increases binding of benzodiazepines, GABA or muscimol in striatum, midbrain (Kendall et al, 1982), cortex (Acuna et al, 1990) and hypothalamus (Majewska et al, 1985;DeSouza et al, 1986). However, the latter may be secondary to a rise in ACTH levels after ADX (Kendall et al, 1982;DeSouza et al, 1986).…”

Concentration Dependent Actions of Glucocorticoids on Neuronal Viability and Survival

“…Generally, GABA exerts an inhibitory activity in the brain and thus can be regarded as an intrinsic neuroprotective factor against excitotoxic brain damage. High concentrations of GCs may deteriorate GABAergic neurotransmission in the brain, as they significantly reduce the efficacy of GABAergic signalling by decreasing the binding of GABA, neurosteroids and benzodiazepines to GABA receptors (Acuna et al 1990; Zeise et al 1992). In fact, electrophysiological measurements on brain slices support the above findings, as the high GC concentrations highly attenuate the generation of GABA A receptor-mediated inhibitory post-synaptic potentials (Joels and De Kloet 1993).…”

Action of Glucocorticoids on Survival of Nerve Cells: Promoting Neurodegeneration or Neuroprotection?1

“…In general terms, GABA exerts inhibitory activity in the CNS and an ‘intrinsic neuroprotective potential’ against excitotoxic brain damage via distinct classes of GABA receptors that are involved in the generation of inhibitory postsynaptic currents. High concentrations of GCs also deteriorate GABAergic neurotransmission in the brain, as they significantly reduce the efficacy of GABAergic signalling by decreasing the binding of GABA, neurosteroids and benzodiazepines to GABA receptors (141, 142). Electrophysiological studies performed on brain slices support the above findings, as the presence of high GC concentrations blocked the generation of GABA A receptor‐mediated inhibitory postsynaptic potentials (143).…”