The inactivation of the basolateral nucleus of the rat amygdala has an anxiolytic effect in the elevated T-maze and light/dark transition tests

Abstract

Pharmacological evidence indicates that the basolateral nucleus of the amygdala (BLA) is involved in the mediation of inhibitory avoidance but not of escape behavior in the elevated T-maze test. These defensive responses have been associated with generalized anxiety disorder (GAD) and panic disorder, respectively. In the present study, we determined whether the BLA plays a differential role in the control of inhibitory avoidance and escape responses in the elevated T-maze. Male Wistar rats (250-280 g, N = 9-10 in each treatment group) were pre-exposed to one of the open arms of the maze for 30 min and 24 h later tested in the model after inactivation of the BLA by a local injection of the GABA A receptor agonist muscimol (8 nmol in 0.2 µL). It has been shown that a prior forced exposure to one of the open arms of the maze, by shortening latencies to withdrawal from the open arm during the test, improves the escape task as a behavioral index of panic. The effects of muscimol in the elevated T-maze were compared to those caused by this GABA agonist in the avoidance reaction generated in the light/dark transition test. This defensive behavior has also been associated with GAD. In the elevated T-maze, intra-BLA injection of muscimol impaired inhibitory avoidance (control: 187.70 ± 14.90 s, muscimol: 37.10 ± 2.63 s), indicating an anxiolytic effect, without interfering with escape performance. The drug also showed an anxiolytic effect in the light/dark transition test as indicated by the increase in the time spent in the lighted compartment (control: 23.50 ± 2.45 s, muscimol: 47.30 ± 4.48 s). The present findings point to involvement of the BLA in the modulation of defensive responses that have been associated with GAD.

Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and anxiety-related responses in rats

“…In fact, the similarities of the role played by the medial hypothalamus and the dPAG in the modulation of defense were previously pointed out by Schmitt et al (8), who showed that both intra-dPAG and intramedial hypothalamus administrations of SR 95103, a GABA-A receptor antagonist, produced a dose-dependent behavioral activation together with jumps. In contrast, the present results do not agree with those observed with another hypothalamic nucleus, the VMHdm (20). Previous observations have shown that muscimol inhibits both ETM-inhibitory avoidance and escape when administered intra-VMHdm.…”

Strychnine and taurine modulation of amygdala-associated anxiety-like behavior is ‘state’ dependent

“…At highest dose used here, taurine (a ~2mM concentration equivalent) could theoretically activate a modest GABA A receptor-mediated current. This dose might therefore produce an initial decrease in neuronal activity and could reduce anxiety-like behavior as is seen with GABA A receptor agonists like muscimol [9]. Although we observed such an anxiolytic effect in our studies, the lower 50pmol (6.3ng) dose produced similar effects but would be expected to produce a 0.1mM concentration equivalent near the injection site, well below that needed to activate either recombinant [15] or native [48] GABA A receptors.…”

“…These data may suggest that the strychnine-sensitive glycine receptors identified using in vitro preparations of this brain region [12,29] function to modulate anxiety-like behaviors in vivo. Previous work has shown that lateral/basolateral amygdala GABA A receptor activation, either directly with agonist [9] or indirectly with benzodiazepine agonist [51], causes anxiolysis while inhibition with receptor antagonists cause anxiogenesis [44]. Given that both glycine and GABA A receptors are ligandgated chloride channels, we initially hypothesized that glycine receptor activation by taurine would also produce anxiolytic effects while inhibition of these receptors by strychnine might produce anxiogenic effects if the receptors were active under the conditions of our behavioral assays.…”

Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder

“…Pharmacological studies have shown that the BLA and central amygdala, in particular, have distinct roles in the anxiolytic effect of benzodiazepines (Green and Vale, 1992). The highest concentration of benzodiazepine receptors appears to be in the BLA (Niehoff and Kuhar, 1983), which is involved in the modulation of inhibitory avoidance, characteristic for anxiety disorders (Bueno et al, 2005). Microinjection studies further support a central role of BLA in the anxiolytic effects of SSRIs (Inoue et al, 2004;Izumi et al, 2006).…”