Effects of Microinjections of a Serotonin Receptor (5-HT 2A/C ) Agonist and Antagonist into the Amygdala in Rats on Anxi
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Effects of Microinjections of a Serotonin Receptor (5-HT2A/C) Agonist and Antagonist into the Amygdala in Rats on Anxiety Behavior and Conditioned Reflex Fear I. V. Pavlova, N. D. Broshevitskaya, and M. P. Rysakova
Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 105, No. 7, pp. 861–878, July, 2019. Original article submitted January 10, 2019. Revised version received March 28, 2019. Accepted April 19, 2019. The role of 5-HT2A/C receptors in the amygdala in the acquisition, testing, and extinction of conditioned reflex fear and on anxiety behavior was studied. Microinjections of a receptor antagonist (ketanserin, 0.5 μg/0.5 μl) into the basolateral nucleus of the amygdala decreased signs of conditioned reflex fear in the form of freezing and prevented reacquisition, but had no effect on anxiety behavior in rats. Administration of an agonist (DOI, 1 μg/0.5 μl) led to an increase in movement activity, panic-like behavior, and decreased anxiety, with reductions in the signs of fear in the form of freezing. Both the agonist and the antagonist of 5-HT2A/C receptors were able to accelerate fear extinction in rats with prolonged freezing, which does not extinguish easily. These results provide evidence that 5-HT2A/C receptors in the amygdala play a significant role in the occurrence and persistence of conditioned reflex fear apparent as freezing. Keywords: amygdala, 5-HT2A/C receptors, agonist, antagonist, anxiety, conditioned reflex fear.
In aversive situations with potential or real threats, animals develop individual/group features of behavior. Tests for anxiety identify low- and high-anxiety individuals, on the basis of the animals’ ability to enter the potentially dangerous sectors of mazes and chambers. Acquisition of a classical defensive reflex (fear conditioning) identifies groups with different durations of freezing – low- and high-reactivity animals [1, 2], and low- and high-freezing rats [3]. Studies of the neurotransmitter mechanisms supporting the different signs and rates of extinction of conditioned reflex fear constitute a relevant task for understanding the patterns of occurrence and regulation of emotional states. Of particular interest is the search for drugs able to influence the behavior of high-anxiety individuals, as well as the rate of extinction and the appearance of fear in animals with high levels of freezing, as such animals can serve as a model of neurotic disorders in humans arising on impairments to fear extinction (for example, anxiety and post-traumatic stress disorder).
According to published data, the basolateral nucleus of the amygdala is a key structure in neural networks supporting both the occurrence and extinction of conditioned reflex fear and anxiety states [4]. The amygdala is under the modulatory influence of the monoaminergic systems, particularly the serotoninergic system. The serotoninergic projections can be followed to the amygdala from the dorsal raphe nucleus of the midbrain [5]. Graeff’s view was that activation of the bottom-up dorsal
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