GABA and Histamine Interaction in the Basolateral Amygdala of Rats in the Plus-Maze Test of Anxiety-Like Behaviors

Abstract

In the present study, we have investigated the effects and the interaction of the GABAergic and histaminergic systems in the basolateral amygdala (BLA) of rats using the plus-maze test of anxiety-like behaviors. Unilateral injection of different doses of muscimol (GABA_A receptor selective agonist; 0.01, 0.05 and 0.1 µg/rat) into the BLA (intra-BLA) increased the percentage of open arm time (%OAT) and open arm entries (%OAE) at the doses of 0.05 and 0.1 µg/rat that are representative of an anxiolytic response. Intra-BLA injection of bicuculline (GABA_A receptor selective antagonist; 0.05, 0.1 and 0.5 µg/rat) decreased %OAT and %OAE at the doses of 0.1 and 0.5 µg/rat showing an anxiogenic-like effect. Intra-BLA administration of histamine (0.05, 0.1 and 0.5 µg/rat) also showed anxiogenic-like effects at the doses of 0.1 and 0.5 µg/rat while intra-BLA administration of pyrilamine (an H₁ receptor selective antagonist; 5, 10 and 20 µg/rat) induced anxiolytic effects at the dose of 20 µg/rat. Coadministration of histamine (0.1 µg/rat) with muscimol reversed the anxiolytic effect of muscimol at the dose of 0.1 µg/rat while coadministration of histamine (0.1 µg/rat) with bicuculline increased the anxiogenic effect of bicuculline at the dose of 0.05 µg/rat. On the other hand, coadministration of pyrilamine (10 µg/rat) with bicuculline decreased anxiety-like behaviors of bicuculline at the dose of 0.5 µg/rat while pyrilamine could not affect the anxiolytic effect of muscimol. In conclusion, it seems that both GABAergic and histaminergic systems not only play a part in the modulation of anxiety-like behaviors in the BLA of rats but may also have opposite effects in this brain region.

Differential Effect of Unilateral Amygdalar GABA<sub>A</sub> Receptor Agonist Injection on Low- and High-Anxiety Rats

“…In agreement with our data regarding anxiolytic effect of muscimol, it had been reported that intra-amygdala injection of the drug increased the percentage of open arm time and open arm entries [28], decreased duration of tonic immobility in guinea pigs [36] and produced anxiolytic-like effects in the social interaction test [29].…”

“…Muscimol hydrobromid (SIGMA) was dissolved in 0.9% saline. Mean muscimol dose leading to anxiolytic-like effect was based on the literature data [28]. Muscimol (0.1 µg/0.5 µl, SIGMA) or saline (control, 0.5 µl) was injected into the right or left basolateral amygdala of HA and LA rats over 2 min.…”

Amygdalar GABAergic-rich neural grafts attenuate anxiety-like behavior in rats

“…Subsequently, Loscher et al showed that GABAergic-rich LGE cell suspension grafts are capable of increasing afterdischarge threshold and decreasing seizure duration and severity in kindled epilepsy [24]. It appears that just as GABAergic grafts attenuated epileptiform activity in a similar manner as infusion of GABA agonists into seizure foci [6, 23], so too have engrafted GABAergic neurons attenuated contextual fear in a similar manner as infusion of GABA agonist within the amygdala [13, 29, 41]. …”

Rearing in enriched environment increases parvalbumin-positive small neurons in the amygdala and decreases anxiety-like behavior of male rats

“…Consequently, excitability of the principal BLA neurons is regulated by these GABAergic neurons [14-18]. Thus, PV-positive neurons are critical for the expression of anxiety-like behavior since activation of PV-positive neurons and pharmacological stimulation of the GABAergic neuronal system in BLA can decrease emotional arousal and anxiety-like behavior [7,19,20]. …”