Role of the amygdala and periaqueductal gray in anxiety and panic

Graeff, Frederico Guilherme; Silveira, Mateus Corrêa; Nogueira, Ricardo de Carvalho; Audi, Elisabeth Aparecida; Oliveira, Rúbia Maria Weffort de

doi:10.1016/0166-4328(93)90097-a

Cited by 279 publications

(141 citation statements)

References 44 publications

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“…DOI fails to elicit anxiolytic-like behavior in mutant mice, whereas the head-twitch response to DOI is reduced less than 50%, suggesting that other mechanisms are equally important for mediating this behavior. It is known that different brain sites mediate these behaviors (Graeff et al, 1993;Willins and Meltzer, 1997), and it is possible that 5-HT 2A receptors within these brain sites are differentially coupled to G protein signaling pathways or that different compensatory mechanisms exist. Importantly, our studies suggest that the G q signaling pathway is required for the full expression of hallucinogeninduced behaviors.…”

Section: Discussionmentioning

confidence: 99%

Role of Gq protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane

2007

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SUMMARYExtensive evidence suggests that 5-HT2 receptors may play a role in mental disorders including schizophrenia. In addition, several studies indicate that G q -coupled 5-HT 2A receptors are likely targets for the initiation of events leading to the hallucinogenic behavior elicited by lysergic acid diethylamide (LSD), (±)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and related drugs. However, 5-HT 2A receptors couple to other G proteins in addition to G q protein. To evaluate the role of the G q signaling pathway in DOI-induced behaviors, we utilized two behavioral models of 5-HT 2A receptor activation: induction of head-twitches by DOI, a common response to hallucinogenic drugs in rodents, and DOI elicited anxiolytic-like effects in the elevated plus maze. Experimental subjects were genetically modified mice [Gα q (−/−)] in which the G q alpha gene was eliminated. Gα q (−/−) mice exhibited a decrease in DOI-induced head-twitches, when compared to wild-type littermates. In addition, the DOI-induced increase in anxiolytic-like behavior was abolished in Gα q (−/−) mice. These results, combined with our finding that DOI-induced FOS expression in the medial prefrontal cortex was also eliminated in Gα q (−/−) mice, suggests a key role for G q protein in hallucinogenic drug effects.

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Section: Discussionmentioning

confidence: 99%

Role of Gq protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane

2007

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“…Graeff et al (1993) have suggested that the elevated plus maze is comparable to aspects of panic disorder in humans. The current observation of altered plus maze performance may be analogous to reports of the development of panic disorder at time points not directly associated with drug use (McCann and Ricaurte 1992;Windhaber et al 1998;Whitaker-Azmitia and Aronson 1989).…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

et al. 2006

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Rationale 3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") use has been associated with acute toxicities and persistent depletion of the neurotransmitter serotonin (5-HT). Objectives This study investigates whether sex differences in the acute and long-term effects of MDMA exist. Methods Male and female rats received saline or 15 mg/kg MDMA, ip, bid for 4 days. Temperature was monitored on days 1 and 4. Locomotor activity was measured in a second cohort of animals on days 1 and 4 and after recovery on day 14. The effects of MDMA on performance in a plus maze task and brain levels of serotonin (5-HT) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were determined in a third cohort of animals 2 weeks after the last MDMA treatment. Results Locomotor activity and temperature increased after MDMA administration on day 1. The drug-induced increases in temperature but not locomotion attenuated with repeated MDMA administration. Male and female MDMA-treated rats spent less time in the open arms of the elevated plus maze and had less 5-HT and 5-HIAA in all brain regions 2 weeks after the end of treatment. Temperature effects of MDMA and persistent effects on plus maze and brain serotonin content were similar in males and females. In contrast, females exhibited markedly greater locomotor stimulation after acute MDMA and also showed sensitization to an acute challenge 2 weeks later. Conclusions MDMA elicits substantially greater locomotor activation in female rats than in males, but persistent effects on anxiety and serotonin content were similar in males and females.

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“…We demonstrated that other structures such as the different amygdaloid nuclei contain V 1b receptors. These brain areas are also known to mediate anxiety-related behaviors observed in the elevated plus-maze or in the punished drinking test (Graeff et al, 1993), suggesting that V 1b receptor located in the amygdala may mediate the anxiolytic effects of SSR149415.…”

Section: Discussionmentioning

confidence: 99%

Evidence that the Lateral Septum is Involved in the Antidepressant-Like Effects of the Vasopressin V1b Receptor Antagonist, SSR149415

Stemmelin

Lukovic

Salomé

et al. 2004

Neuropsychopharmacol

104

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Previous experiments with the first selective nonpeptide vasopressin V 1b receptor antagonist SSR149415 ((2S, 4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide) have shown that the drug elicits anxiolytic-and antidepressant-like effects following systemic administration. Extrahypothalamic V 1b receptors have been suggested to be involved in these effects as evidenced by the findings that hypophysectomized rats were still sensitive to the antistress action of SSR149415. The first objective of the present work aimed at locating V 1b receptors in the rat limbic brain using anti-V 1b receptor immunohistochemistry. The immunolabeling revealed high densities of V 1b receptors in the lateral septum, the amygdala, the bed nucleus of the stria terminalis, the hippocampal formation, and in several cortical areas. Since the lateral septum is well known to participate in the modulation of emotional processes, the second objective of this study went on to evaluate the behavioral effects of an infusion of SSR149415 into the lateral septum and to determine whether its behavioral effects are mediated by this structure. Animals were tested in models classically used for the screening of anxiolytics (ie the punished drinking and elevated plusmaze tests) and antidepressants (ie the forced-swimming test). Bilateral intraseptal infusion of SSR149415 (10 and 100 ng) produced a decrease in immobility time in the forced-swimming test, indicating antidepressant-like effects. In contrast, the behavior of rats in the punished drinking procedure or in the elevated plus-maze test was not modified by intraseptal infusion of SSR149415. These findings suggest that V 1b receptors located in the lateral septum participate in the antidepressant-but not the anxiolytic-like action of SSR149415 in rats.

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Role of the amygdala and periaqueductal gray in anxiety and panic

Cited by 279 publications

References 44 publications

Role of Gq protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane

Role of Gq protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane

Sex differences in the neurochemical and functional effects of MDMA in Sprague–Dawley rats

Evidence that the Lateral Septum is Involved in the Antidepressant-Like Effects of the Vasopressin V1b Receptor Antagonist, SSR149415

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