Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

This paper presents an up-to-date review of the evidence indicating that atypical neurotransmitters such as nitric oxide (NO) and endocannabinoids (eCBs) play an important role in the regulation of aversive responses in the periaqueductal gray (PAG). Among the results supporting this role, several studies have shown that inhibitors of neuronal NO synthase or cannabinoid receptor type 1 (CB1) receptor agonists cause clear anxiolytic responses when injected into this region. The nitrergic and eCB systems can regulate the activity of classical neurotransmitters such as glutamate and γ-aminobutyric acid (GABA) that control PAG activity. We propose that they exert a ‘fine-tuning’ regulatory control of defensive responses in this area. This control, however, is probably complex, which may explain the usually bell-shaped dose-response curves observed with drugs that act on NO- or CB1-mediated neurotransmission. Even if the mechanisms responsible for this complex interaction are still poorly understood, they are beginning to be recognized. For example, activation of transient receptor potential vanilloid type-1 channel (TRPV1) receptors by anandamide seems to counteract the anxiolytic effects induced by CB1 receptor activation caused by this compound. Further studies, however, are needed to identify other mechanisms responsible for this fine-tuning effect.

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9 percent saline, ethyl alcohol, Emulphor® (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

Anandamide injected into the lateral ventricle of the brain inhibits submandibular salivary secretion by attenuating parasympathetic neurotransmission

Our objective was to determine the effect of arachidonylethanolamide (anandamide, AEA) injected intracerebroventricularly (icv) into the lateral ventricle of the rat brain on submandibular gland (SMG) salivary secretion. Parasympathetic decentralization (PSD) produced by cutting the chorda tympani nerve strongly inhibited methacholine (MC)-induced salivary secretion while sympathetic denervation (SD) produced by removing the superior cervical ganglia reduced it slightly. Also, AEA (50 ng/5 µL, icv) significantly decreased MC-induced salivary secretion in intact rats (MC 1 µg/kg: control (C), 5.3 ± 0.6 vs AEA, 2.7 ± 0.6 mg; MC 3 µg/kg: C, 17.6 ± 1.0 vs AEA, 8.7 ± 0.9 mg; MC 10 µg/kg: C, 37.4 ± 1.2 vs AEA, 22.9 ± 2.6 mg). However, AEA did not alter the significantly reduced salivary secretion in rats with PSD, but decreased the slightly reduced salivary secretion in rats with SD (MC 1 µg/kg: C, 3.8 ± 0.8 vs AEA, 1.4 ± 0.6 mg; MC 3 µg/kg: C, 14.7 ± 2.4 vs AEA, 6.9 ± 1.2 mg; P < 0.05; MC 10 µg/kg: C, 39.5 ± 1.0 vs AEA, 22.3 ± 0.5 mg; P < 0.001). We showed that the inhibitory effect of AEA is mediated by cannabinoid type 1 CB1 receptors and involves GABAergic neurotransmission, since it was blocked by previous injection of the CB1 receptor antagonist AM251 (500 ng/5 µL, icv) or of the GABA A receptor antagonist, bicuculline (25 ng/5 µL, icv). Our results suggest that parasympathetic neurotransmission from the central nervous system to the SMG can be inhibited by endocannabinoid and GABAergic systems.

Effect of dietary supplementation of active EPA-30 on the phospholipid metabolism in the rat liver

To explore the useness of fish oil [active EPA-30] as a source of eicosapentenoic acid [EPA, 20: 5 n-3], the studies were performed on a total of 120 rats, divided into 2 equal groups. The results showed that, the young rats fed on pig-fat [n-3 fatty acids deficient diets] had a drastic decrease in the amount of phosphatidylethanolamine [PE] and omega-3 polyunsaturated fatty acids [eicosapentenoic, EPA, 20: 5 n-3 and docosahexenoic, DHA, 22: 6 n-3] and compensatory increase of phosphotidylcholine, saturated fatty acids and n-6 polyunsaturated fatty acids in the phospholipids of their liver. In contrast, the rats fed on active EPA-30 has large amounts of PE and complementary enrichment with polyunsaturated fatty acids. While the old rats, supplemented with active EPA-30 had lowest amounts of PE and there is no any significant changes in the phospholipid fatty acid compositions

A novel property of an aqueous guaraná extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo

Aqueous extracts of guaraná were studied in terms of effects on the aggregation of human and rabbit platelets. Guaraná extracts have anti-aggregatory and de-aggregatory actions on platelet aggragation induced by ADP or arachidonate but not by collagen. The active material was shown to be water soluble and heat resistant and appeared to be different from salicylates, nicotinic acid or known xanthines. Guaraná extracts inhibited platelet aggregation in rabbits following either intravenous or oral administration

Derivados del ácido araquidónico. II. Perspectivas médicas / Arachidonic acid derivatives. II. Medical perspectives

En esta segunda parte, se analiza la relación existente entre derivados del ácido araquidónico y regulación de la función de los leucocitos, incluyendo las acciones de estos compuestos sobre diferentes poblaciones celulares que participan en la respuesta inmune. Se analizan los diferentes fármacos inhibidores (esteroidales y no esteroidales) de la síntesis de los derivados del ácido araquidónico y algunas perspectiva para su uso. Finalmente, se consideran aquellos cuadros patológicos en donde la participación de los derivados del ácido araquidónico juega un rol significativo, ya sea produciendo el fenómeno patogénico y/o sirviendo de blanco terapéutico para la modificación del evento patológico

Efectos de sulfinpirazona sobre tejidos miocárdicos con estimulación eléctrica o sin ella / Effects of sulfinpyrazone on myocardial tissues with or without electrical stimulation

Se estudiaron in vitro los efectos del ácido arquidónico (AAq) y sulfinpirazona (SP) sobre miocardio de rata "suquía" de 240+ ou - 10g. Bandas auriculares y ventriculares fueron instaladas en solución Krebs-bicarbonato a 36 + ou- 1-C, registrado tensión contráctil isométrica (TC) y niveles de malonato (MDA), con electroestimulación o sin ella (1,6 Hz), AAq (2,5 microng/ml) y SP (375, 750, 1.500 y 3.000 microng/ml). AAq deprimió 100% de la TC de ambos preparados, registrándose en tiempos variables (9 a 17 min.) recuperación espontánea en la mayoría de los casos, aunque sin recuperar los valores iniciales. La reactividad eléctrica aumentó en el tejido auricular, pero no en el ventricular. Los efectos de SP dependen de la concentración; 375 microng/ml bajan la TC auricular 87 + ou - 7,3%. La respuesta ventricular a esa dosis fue variable, aunque la TC disminuyó en 61,5% de los preparados; 3 mg/ml son homogéneamente estimulantes. La reactividad eléctrica disminuye con SP. La concentración de MDA en los preparados auriculares cayó muy significativamente (p<0,001) después de SP. En los ventriculares se observó disminución de menor magnitud, también significativa (p<0,02). La suma algebraica de caída y recuperación de TC de los preparados auriculares después de dar SP, da un porcentaje de pérdida similar al descenso del malonato (+ ou - 25%). Se sugiere que: a) AAq deprime el miocardio por acción directa sin descartar alguna transformación inmediata en derivados activos. b) La SP inhibiría distintas enzimas en función de las dosis. c) El MDA parece ser consumido por el tejido miocárdico o metabolizado en el medio. Se plantean explicaciones alternativas para este fenómeno y su relación con el mecanismo de acción de la sulfinpirazona