Distinct effect of 5-HT1A and 5-HT2A receptors in the medial nucleus of the amygdala on tonic immobility behavior

Abstract

The tonic immobility (TI) response is an innate fear behavior associated with intensely dangerous situations, exhibited by many species of invertebrate and vertebrate animals. In humans, it is possible that TI predicts the severity of posttraumatic stress disorder symptoms. This behavioral response is initiated and sustained by the stimulation of various groups of neurons distributed in the telencephalon, diencephalon and brainstem. Previous research has found the highest Fos-IR in the posteroventral part of the medial nucleus of the amygdala (MEA) during TI behavior; however, the neurotransmission of this amygdaloid region involved in the modulation of this innate fear behavior still needs to be clarified. Considering that a major drug class used for the treatment of psychopathology is based on serotonin (5-HT) neurotransmission, we investigated the effects of serotonergic receptor activation in the MEA on the duration of TI. The results indicate that the activation of the 5HT1A receptors or the blocking of the 5HT2 receptors of the MEA can promote a reduction in fear and/or anxiety, consequently decreasing TI duration in guinea pigs. In contrast, blocking the 5HT1A receptors or activating the 5HT2 receptors in this amygdalar region increased the TI duration, suggesting an increase in fear and/or anxiety. These alterations do not appear to be due to a modification of spontaneous motor activity, which might non-specifically affect TI duration. Thus, these results suggest a distinct role of the 5HT receptors in the MEA in innate fear modulation.

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

“…Besides 5-HT 2A receptors, MDMA does bind with notably weaker affinity as a partial agonist at 5-HT 1A and 5-HT 2C receptor sites (Battaglia et al 1988). Interestingly, 5-HT 1A agonists have been observed to acutely reduce the expression of conditioned fear (de Paula and Leite-Panissi 2016; Risbrough et al 2003), while antagonists block the psychomotor stimulant and pro-social effects of MDMA in mice (Hunt et al 2011; Morley et al 2005). Given the proposed role of therapeutic alliance in the effect of MDMA on PTSD psychotherapy, it is possible that 5-HT 1A signaling is important in clinical context.…”

Serotonin distinctly controls behavioral states in restrained and freely moving Drosophila

“…5-HT7 receptors have been implicated in various psychological disorders. 17 , 61 , 62 Interestingly, 5-HT7 antagonists also exert antidepressant-like effects in the forced swim test. 63 However, in our study, we observe that 5-HT7 receptor mutant flies show enhanced STRIF-immobility, which contradicts what has been reported earlier in mice.…”

Case Report: GABAergic and Serotoninergic Agents for the Treatment and Prevention of Prolonged Dissociative Stupor

“…For instance, activation of 5-HT 1A receptors or blockade of 5-HT 2 receptors in the MEA decreased TI duration in guinea pigs. In contrast, blocking 5HT 1A receptors or activating 5-HT 2 receptors in the amygdala increased the duration of TI ( 14 ) ( Figure 2 ). It must be noted that two of the three confirmed stupors resolved spontaneously; moreover, this is a single case report, thus remaining rather speculative.…”