Dorsal hippocampal galanin modulates anxiety-like behaviours in rats.

Galanin, a peptide expressed in mammalian brain regions, has been implicated in anxiety and depression. Galanin signalling occurs through three G protein-linked receptors (GAL1, GAL2 and GAL3). Galanin regulates the release of neurotransmitters in some brain regions related to anxiety, including the hippocampus. GAL2 is the most abundant galanin receptor in the dorsal hippocampus. In this study, we evaluated whether galanin administered in the dorsal hippocampus affected anxiety-like behaviours of rats. We also investigated if GAL2 receptors are involved in the anxiogenic-like effect of galanin using a GAL2 antagonist, M871. To achieve these objectives, male adult Wistar rats received intra-dorsal hippocampal delivery of galanin (0.3 and 1.0 nmol/0.5 µl) or vehicle in experiment 1 and GAL2 antagonist M871 (1.0 and 3.0 nmol/0.5 µl) or vehicle in experiment 2. Twenty min after administration of drugs, the animals were tested in the elevated plus-maze (EPM). Galanin (1.0 nmol) induced anxiogenic-like behaviours, while the GAL2 receptor antagonist M871 (3.0 nmol) induced anxiolytic-like behaviours in rats exposed to the EPM, indicating a tonic effect of galanin. In experiment 3, we evaluated whether previous infusion of the GAL2 antagonist M871 (1 or 2 nmol) in the dorsal hippocampus would block the anxiogenic-like effect of galanin in rats tested in the EPM. We showed that M871 (2.0 nmol) counteracted the anxiogenic-like effect of galanin infused in the dorsal hippocampus of rats. Altogether, our results provide evidence that galanin promotes pharmacological and tonic anxiogenic-like effects in the dorsal hippocampus, possibly mediated by GAL2 receptors.

Contrasting effects of Na+, K+-ATPase activation on seizure activity in acute versus chronic models.

Epilepsy is a life-shortening brain disorder affecting approximately 1% of the worldwide population. Most epilepsy patients are refractory to currently available antiepileptic drugs (AEDs). Knowledge about the mechanisms underlying seizure activity and probing for new AEDs is fundamental to the discovery of new therapeutic strategies. Brain Na(+), K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. Accordingly, a decrease of Na(+), K(+)-ATPase increases neuronal excitability and may predispose to appearing of seizure activity. In the present study, we tested the hypothesis that activation of Na(+), K(+)-ATPase activity with a specific antibody (DRRSAb) raised against a regulatory site in the α subunit would decrease seizure susceptibility. We found that incubation of hippocampal homogenates with DRRSAb (1 µM) increased total and α1 Na(+), K(+)-ATPase activities. A higher concentration (3 µM) increased total, α1 and α2/α3 Na(+), K(+)-ATPase activities. Intrahippocampal injection of DRRSAb decreased the susceptibility of post status epilepticus animals to pentylenetetrazol (PTZ)-induced myoclonic seizures. In contrast, administration of DRRSAb into the hippocampus of naïve animals facilitated the appearance of PTZ-induced seizures. Quantitative analysis of hippocampal electroencephalography (EEG) recordings revealed that DRRSAb increased the percentage of total power contributed by the delta frequency band (0-3 Hz) to a large irregular amplitude pattern of hippocampal EEG. On the other hand, we found no DRRSAb-induced changes regarding the theta functional state. Further studies are necessary to define the potential of Na(+), K(+)-ATPase activation as a new therapeutic approach for seizure disorders.