Extracellular Hypothalamic γ-Aminobutyric Acid (GABA) and L-Glutamic Acid Concentrations in Response to Bicuculline in a Genetic Absence Epilepsy Rat Model

Abstract

Abstract. The posterior part of the hypothalamus plays a vital role in the homeostatic processes of the internal environment, including blood pressure and heart rate regulation, by means of γ-aminobutyric acid (GABA)ergic and glutamatergic neurotransmission. In this study we measured the extracellular levels of GABA and L-glutamic acid in the dorsomedial hypothalamic nucleus (DMH) and posterior hypothalamus (PH), following intracerebroventricular (i.c.v.) administration of bicuculline, a GABA A -receptor antagonist, in genetic absence epileptic rats from Strasbourg (GAERS), where heart rate, blood pressure, and EEG recordings were also collected simultaneously. The i.c.v. injection of bicuculline (0.3 nmol) produced no response in nonepileptic Wistar rats but caused an increase in mean arterial pressure in GAERS (P<0.01). Microdialysis experiments showed that L-glutamic acid increased in the DMH in GAERS after bicuculline administration (P<0.01). Additionally, extracellular GABA concentration decreased in the PH (P<0.05). Bicuculline suppressed the spike-and-wave discharges, the characteristic sign of absence seizures. All these results suggest that the bicuculline-induced blood pressure response is accompanied by changes in L-glutamic acid levels in the DMH and GABA levels in the PH, indicating a bicuculline hypersensitivity in the DMH and PH of GAERS that may make the GAERS display an altered mode of central cardiovascular regulation. These results suggest that the circuits affected in GAERS are not only restricted to the regions responsible for seizure generation but also present in the hypothalamus.

GABAB receptor‐mediated frequency‐dependent and circadian changes in synaptic plasticity modulate retinal input to the suprachiasmatic nucleus

“…Therefore, presynaptic GABA B Rs on RHT terminals could be activated by GABA that diffuses from local GABAergic synapses (Moore & Speh, 1993; Sollars et al 2006; Belenky et al 2008) including afferents from the intergeniculate leaflet (Pickard et al 1987; Morin et al 1992) and surrounding hypothalamic tissue (Castel & Morris, 2000). The extracellular GABA concentration in the hypothalamus was detected by microdialysis in the range 0.05–0.07 μ m (Yananli et al 2008). The low endogenous GABA concentration and, therefore relatively weak activation of GABA B Rs might explain why microinjection of GABA B antagonists neither alters phase shifts during the subjective night or increases c‐Fos expression in the SCN when administered before light exposure, nor induce phase shifts when given alone (Gillespie et al 1997, 1999).…”

Restoration of the Luteinizing Hormone Surge in Middle-Aged Female Rats by Altering the Balance of GABA and Glutamate Transmission in the Medial Preoptic Area1

“…al. [72], who showed that intracerebral bicuculline infusion increases Glu and decreases GABA release. Our observations are also consistent with other reports of age-related changes in the expression of Gad1 mRNA [6, 67] and increases in GAD1 activity [67].…”

Angiotensin II and its receptor in activated microglia enhanced neuronal loss and cognitive impairment following pilocarpine-induced status epilepticus

“…All drug solutions were prepared fresh daily. Intracerebroventricular administration was performed as described previously (Sun et al, 2013;Yananli et al, 2008). Briefly, the rats were fixed in a stereotaxic frame, anesthetized, and a midline incision was made along the scalp.…”