Serotonina, matéria cinzenta periaquedutal e transtorno do pânico

Abstract

This article reviews experimental evidence and theoretical constructs that implicate serotonin (5-HT) modulation of defensive behavior within the midbrain periaqueductal gray matter(PAG) in panic disorder. Results obtained with conflict tests in experimental animals indicate that 5-HT enhances anxiety, whereas results with aversive stimulation of the dorsal PAG point to an anxiolytic role of 5-HT. To solve this contradiction, it has been suggested that the emotional states determined by the two paradigms are different. Conflict tests would generate anticipatory anxiety, whereas PAG stimulation would produce fear as evoked by proximal threat. Clinically, the former would be related to generalized anxiety while the latter to panic disorder. Thus, 5-HT is supposed to facilitate anxiety, but to inhibit panic. This hypothesis has been tested in the animal model of anxiety and panic named the elevated T-maze and in two procedures of human experimental anxiety applied to healthy volunteers or panic patients. Overall, the obtained results have shown that drugs that enhance 5-HT action increase different indexes of anxiety, but decrease indexes of panic. Drugs that impair 5-HT action had the opposite effects. Thus, so far the predictions derived from the above hypothesis have been fulfilled. The main clinical implications are that a 5-HT deficit in the PAG may participate in the pathophysiology of panic disorder and that an enhancement of 5-HT in the same region mediates the anti-panic action of antidepressant drugs.

Intrauterine Exposure to Chronic 22 kHz Sound Affects Inhibitory Avoidance and Serotonergic Parameters in Forebrain Areas of Dams and Rat Offspring

“…These data suggest that there might be a relation between 22 kHz sound and the neurobiological substrate of inhibitory avoidance but no association with escape. Likewise, the fear and anxiety behavior have different effects on the serotonergic system [56] [57].…”

Evidences for the Anti-panic Actions of Cannabidiol

“…In humans, responses related to PD have been assessed in both healthy volunteers and panic patients submitted to controlled conditions of psychological or chemical-nature stimuli [15, 16]. For instance, in the simulated public speaking (SPS) test, the participant must prepare a speech and talk in front of a video camera [17].…”

“…Classical benzodiazepines decrease the VAMS indices before and after the speech, without affecting speech preparation or performance (which is associated with “fear of speaking”). Conversely, speech preparation and performance are reduced by antidepressants [15]. Based on pharmacological studies, it has been proposed that the neural networks activated by SPS are involved in anxiety disorders [16] and, thus, that the fear of speaking provoked by the SPS test can be helpful in understanding the brain areas involved and potential new drugs targets for PD.…”

Avaliação da ativação da via HO-CO-GMPc do locus coeruleus na modulação da ansiedade e da nocicepção em ratos.

“…Em adição, outras estruturas límbicas tais como o córtex pré-frontal, tálamo e corpos mamilares, atuam em conjunto com o sistema septo-hipocampal. Ao SIC, acrescenta-se ainda a amígdala como estrutura responsável pela avaliação do componente afetivo em situações de conflito (Graeff & Zangrossi, 2002;Graeff, 2003). A propósito, Gray & McNaughton (2000) sugeriram que a função principal do SIC é de detectar o conflito.…”

“…No medo, não há tendência de aproximação da fonte de perigo, mas somente a de afastar dela ou evitá-la. Um segundo sistema de modulação das respostas emocionais é descrito tendo como eixo a substância cinzenta periaquedutal (SCP), o hipotálamo e a amígdala, denominado de Sistema Cerebral Aversivo (SCA) (Graeff, 2003). De fato, estudos pioneiros mostraram que a estimulação elétrica ou química dessas estruturas evocava padrões comportamentais defensivos espécie-específicos e, comportamentos sugestivos de experiência aversiva prévia (Olds & Olds, 1962 (Graeff, 2002).…”