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1.
Neurosci Lett ; 729: 135018, 2020 06 11.
Article in English | MEDLINE | ID: mdl-32360933

ABSTRACT

Several studies suggest the involvement of glutamatergic neurotransmission in obsessive-compulsive disorder (OCD). Some NMDA glutamatergic receptor antagonists, such as the general anesthetic ketamine, have shown anti-OCD effects in preclinical and clinical studies. Therefore, we investigated whether the inhalational anesthetics isoflurane and sevoflurane, which are general anesthetics acting as NMDA receptor antagonists, would induce the same effects. To test our hypothesis, adult male Swiss mice were exposed to different concentrations of isoflurane (0.5, 1.5 or 3 %) or sevoflurane (0.8, 2.5 or 4 %) for 20 min (short-time exposure) or 1 h (moderate-time exposure) and submitted to the open field test (OFT) and the marble-burying test (MBT) in the same day (acute effect) or 7 days (long-lasting effect) after anesthetics administration. We found that single short or moderate-time exposure to isoflurane or sevoflurane, at sub-anesthetic or anesthetic concentrations, did not affect marble-burying behavior acutely or even 7 days after their administration. The same treatment schedules with isoflurane or sevoflurane did not impair total distance travelled in the OFT. A single moderate-time exposure to isoflurane (3 %) reduced, acutely, the central exploration of the open field, suggesting an anxiogenic-like effect of isoflurane in mice. Our results suggest that isoflurane and sevoflurane may not be promising anti-compulsive drugs.


Subject(s)
Anesthetics, Inhalation/pharmacology , Behavior, Animal/drug effects , Motor Activity/drug effects , Sevoflurane/pharmacology , Animals , Calcium Carbonate/pharmacology , Isoflurane/pharmacology , Male , Methyl Ethers/pharmacology , Mice , Time Factors
2.
Neurosci Lett ; 681: 26-30, 2018 08 10.
Article in English | MEDLINE | ID: mdl-29787787

ABSTRACT

Galanin is a neuropeptide distributed in human and rat brain regions that are involved with emotional regulation, such as the dorsal raphe nucleus (DRN). Galanin effects in the DRN are mediated by GAL1 and GAL2 receptors. Intracerebral infusion of a GAL2 (AR-M1896) or a GAL1 (M617) agonist induced either antidepressant or depressive-like effect, respectively, in rats exposed to the forced swimming test (FST). However, it is not clear if GAL1 and/or GAL2 receptors present in the DRN would be involved in such effects. Therefore, we investigated the effects induced by intra-DRN infusion of galanin (0.3 nmol), AR-M1896 (1 nmol, GAL2 agonist), or M617 (GAL1 agonist) in rats exposed to the FST. Galanin and AR-M1896 intra-DRN administration induced antidepressant-like effect in the FST. However, M617 did not induce any change in the FST. Neither M617 nor AR-M1896 changed the locomotor activity of rats in the open field test. Intra-DRN pre-treatment with M871 (1 nmol), a selective GAL2 antagonist, counteracted the antidepressant-like effect induced by galanin. These results suggest that galanin signaling through GAL2 receptors in the DRN produces triggers antidepressant-like effect.


Subject(s)
Antidepressive Agents/administration & dosage , Depression/drug therapy , Dorsal Raphe Nucleus/physiology , Galanin/administration & dosage , Protein Precursors/administration & dosage , Receptor, Galanin, Type 2/physiology , Animals , Depression/psychology , Dorsal Raphe Nucleus/drug effects , Injections, Intraventricular , Male , Peptide Fragments/administration & dosage , Peptides/administration & dosage , Rats , Rats, Wistar , Receptor, Galanin, Type 2/agonists , Receptor, Galanin, Type 2/antagonists & inhibitors , Swimming/physiology , Swimming/psychology , Treatment Outcome
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