Antidepressant-like effect of valproic acid-Possible involvement of PI3K/Akt/mTOR pathway.

Rationale: Few studies suggest that antidepressants exert their effects by activating some signaling pathways, including the phosphatidylinositol 3-kinase (PI3K). Moreover, valproic acid (VPA) activates the PI3K pathway. Thus, here we investigated the antidepressant-like effect of VPA and if its effect is related to PI3K/Akt/mTOR activation.

Blockade of NMDA or NO in the dorsal premammillary nucleus attenuates defensive behaviors.

The dorsal premammillary nucleus (PMd) is a hypothalamic structure that plays a pivotal role in the processing of predatory threats. Lesions of this nucleus virtually eliminate the expression of defensive responses to predator exposure. However, little is known about the neurotransmitters responsible for these behavioral responses.

NOC-9, a selective nitric oxide donor, induces flight reactions in the dorsolateral periaqueductal gray of rats by activating soluble guanylate cyclase.

Previous studies have showed that SIN-1, a nitric oxide (NO) donor, injected into the dorsolateral column of the periaqueductal gray (dlPAG) induces flight reactions. This drug, however, can also produce peroxynitrite, which may interfere in this effect. In addition, it is also unknown if this effect is mediated by local activation of soluble guanylate cyclase (sGC).

Blockade of NMDA receptors and nitric oxide synthesis in the dorsolateral periaqueductal gray attenuates behavioral and cellular responses of rats exposed to a live predator.

Innate fear stimulus induces activation of neurons containing the neuronal nitric oxide synthase enzyme (nNOS) in defensive-related brain regions such as the dorsolateral periaqueductal gray (dlPAG). Intra-dlPAG administration of nitric oxide synthase (NOS) inhibitors and glutamate antagonists induce anxiolytic-like responses. We investigated the involvement of nitric oxide (NO) and glutamate neurotransmission in defensive reactions modulated by dlPAG.

Anxiolytic-like effect of cannabinoids injected into the rat dorsolateral periaqueductal gray.

Contradictory results exist concerning the effects of systemic injections of CB(1) cannabinoid receptor agonists on anxiety-related behaviors. Direct drug administration into brain structures related to aversive responses can potentially help to clarify the role of cannabinoids on anxiety. One such structure is the midbrain dorsolateral periaqueductal gray (dlPAG).

Flight reactions induced by injection of glutamate N-methyl-d-aspartate receptor agonist into the rat dorsolateral periaqueductal gray are not dependent on endogenous nitric oxide.

Glutamate N-methyl-d-aspartate (NMDA) receptors and the enzyme neuronal nitric oxide synthase (nNOS) are significantly expressed in the midbrain dorsolateral periaqueductal gray (dlPAG). Local injections of either NMDA-receptor agonists or nitric oxide (NO) donors induce flight reactions in rats. Since the activation of NMDA receptors in the brain increases the synthesis of NO, the present work was conducted to test the hypothesis that the flight reaction induced by intra-dlPAG administration of NMDA would be mediated by endogenous NO.