RESUMO
Systemic injection of the cholecystokinin type 2 (CCK(2)) receptor agonist CCK-4 evokes panic attacks in humans and facilitates the expression of a panic-related defensive behavior, escape, in rats. Given the prominent role attributed to the dorsal periaqueductal gray (dPAG) in the pathophysiology of panic, this midbrain area has been assumed to be one of the key regions mediating these effects of CCK-4. However, only a few studies have directly investigated the role of dPAG CCK(2) receptors in the regulation of panic-related behaviors. Even more disappointingly, the results of these investigations have been far from conclusive. In the present study we further addressed this issue by evaluating the effect of the intra-dorsolateral periaqueductal gray (dlPAG) injection of CCK-4 on two panic-related defensive behaviors, freezing and escape, evoked in male Wistar rats by the electrical stimulation of the dlPAG. The effects of CCK-4 (0.005-0.5 microg/0.2 microl) were compared to those caused by the local microinjection of the CCK(2) receptor antagonist LY225910 (0.001-1.0 microg/0.2 microl). The results showed that whereas CCK-4 facilitated the expression of both freezing and escape behaviors, LY225910 had the opposite effect. Pretreatment with an ineffective dose of LY225910 prevented the panicogenic-like effect of CCK-4. These results strengthen the view that CCK(2) receptors located in the dlPAG are involved in the regulation of panic-related behaviors and may mediate the effect of CCK-4 on panic.
Assuntos
Reação de Fuga/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Receptor de Colecistocinina B/fisiologia , Tetragastrina/farmacologia , Animais , Estimulação Elétrica , Reação de Fuga/efeitos dos fármacos , Congelamento , Lateralidade Funcional , Microinjeções , Pânico/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Quinazolinonas/farmacologia , Ratos , Receptor de Colecistocinina B/antagonistas & inibidores , Tetragastrina/administração & dosagemRESUMO
Several neurotransmitters, including GABA, serotonin, glutamate, and cholecystokinin, modulate defensive behaviors in the dorsolateral periaqueductal gray (dlPAG). Although both glutamate and cholecystokinin have been shown to facilitate these behaviors, a possible interaction between them remains to be examined. The present study investigates whether activation or antagonism of N-methyl-D-aspartic acid (NMDA) glutamate and cholecystokinin 2 (CCK(2)) receptors located in the dlPAG would interact in animals tested in the elevated T-maze. The effect of the NMDA (50 pmol) was evaluated in rats pretreated with the CCK(2) receptor antagonist LY225910 (0.05 nmol). In addition, the effect of the CCK(2) receptor agonist CCK-4 (0.08 nmol) was evaluated in rats pretreated with the NMDA receptor antagonist AP-7 (1.0 nmol). Intra-dlPAG injection of NMDA increased risk assessment and inhibitory avoidance behaviors. This NMDA anxiogenic-like effect was unaltered by the pretreatment with LY225910. Similarly, the shortening of escape latencies induced by CCK-4 was unaffected by AP-7. No drug changed the general exploratory activity as assessed in the open-field. These results, showing that the activation of dlPAG NMDA or CCK(2) receptors facilitate anxiety- and fear-related behaviors, further implicate glutamate and cholecystokinin-mediated neurotransmission in this midbrain area on modulation of defensive behaviors. However, the regulatory action of these two excitatory neurotransmitters seems to be exerted through independent mechanisms.
Assuntos
Comportamento Animal/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , N-Metilaspartato/farmacologia , Substância Cinzenta Periaquedutal/metabolismo , Receptor de Colecistocinina B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , 2-Amino-5-fosfonovalerato/análogos & derivados , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Relação Dose-Resposta a Droga , Fármacos Gastrointestinais/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Quinazolinonas/farmacologia , Ratos , Ratos Wistar , Receptor de Colecistocinina B/metabolismo , Tetragastrina/farmacologiaRESUMO
Cholecystokinin (CCK) has been implicated in anxiety disorders. The midbrain periaqueductal gray (PAG), which modulates anxiety and panic reactions, contains CCK-immunoreactive fibers and CCK(2) receptors. The present study investigated the involvement of CCK(2) receptors of the PAG dorsolateral subdivision (dlPAG) in the regulation of inhibitory avoidance and escape, two defensive behaviors that have been related in terms of psychopathology to generalized-anxiety and panic disorders, respectively. Male Wistar rats were microinjected in the dlPAG with the CCK(2) receptor agonist cholecystokinin-tetrapeptide (CCK-4; 0.08-0.32 nmol/0.2 microL), the CCK(2) receptor antagonist LY-225910 (0.05-0.20 nmol/0.2 microL) or LY-225910 prior to CCK-4. Inhibitory avoidance and escape behaviors were evaluated in the elevated T-maze. Whereas CCK-4 facilitated escape, indicating a panic-like action, LY-225910 had the opposite effect. Pretreatment with a non-effective dose of LY-225910 prevented the panic-eliciting action of CCK-4. Neither CCK-4 nor LY-225910 affected inhibitory avoidance acquisition. The present results substantiate the view that dlPAG CCK(2) receptors modulate panic-related behaviors.
Assuntos
Colecistocinina/metabolismo , Vias Neurais/metabolismo , Transtorno de Pânico/metabolismo , Substância Cinzenta Periaquedutal/metabolismo , Receptor de Colecistocinina B/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Medo/efeitos dos fármacos , Medo/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Vias Neurais/efeitos dos fármacos , Transtorno de Pânico/induzido quimicamente , Transtorno de Pânico/fisiopatologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Quinazolinas/farmacologia , Quinazolinonas , Ratos , Ratos Wistar , Receptor de Colecistocinina B/agonistas , Receptor de Colecistocinina B/antagonistas & inibidores , Tetragastrina/farmacologiaRESUMO
Stereotyped behavior can be induced by the dopamine agonist apomorphine or by the releasing agent amphetamine. Cholecystokinin influence on dopamine-mediated behaviors has been extensively studied but a real controversy remains. Our purpose was to further characterize the dopamine-cholecystokinin interaction in apomorphine- and amphetamine-induced stereotyped behavior using sulphated cholecystokinin octapeptide (CCK8) and cholecystokinin tetrapeptide (CCK4) treatments. The results showed that CCK8 decreases apomorphine-induced stereotyped behavior and CCK4 has no effect. CCK4 and CCK8 increased the amphetamine-induced stereotyped behavior; CCK4 was more effective. The results confirm the opposite modulation of apomorphine or amphetamine-induced stereotyped behavior by CCK. These data suggest that this modulation is mediated by both CCK receptors on apomorphine-induced and only by CCK(2) receptors on amphetamine-induced stereotyped behavior.
Assuntos
Anfetaminas/farmacologia , Apomorfina/farmacologia , Colecistocinina/farmacologia , Agonistas de Dopamina/farmacologia , Dopamina/metabolismo , Interações Medicamentosas , Animais , Masculino , Ratos , Ratos Wistar , Receptores da Colecistocinina/metabolismo , Sincalida/farmacologia , Sinapses/efeitos dos fármacos , Tetragastrina/farmacologia , Fatores de TempoRESUMO
This study is concerned with electron-microscopic observations on endocrine or paracrine cells in the fundic gastric mucosa of the bullfrog. Also, an attempt was made to identify the histamine-releasing cells involved in the secretagogue response. At least three distinct endocrine-like cell types were found. The classification is based on the appearance of secretory granules and other organelles, and the relationship of endocrine-like cells with other cells in the tissue. The amphibian endocrine-like cells resemble the ECL, D and EC cells of mammals. Type-I (ECL) cells showed degranulation after repeated stimulation with tetragastrin (TG), acetylcholine (ACh) and K+ depolarizing solution, all of which release histamine.