Objective(s): Several lines of evidence indicate that neuropeptides exhibit protective properties against gastro duodenal ulcers. Neurotensin, a gut-brain neuropeptide, is implicated in a number of physiological processes in the central nervous system and peripheral tissues including gastrointestinal tract. In the present study, we aimed to investigate the gastro protective potential of either peripherally or centrally administered neurotensin with a look at the role of the cannabinoid CB1 receptors which are located in brain areas implicated in the regulation of gastric functions. Materials and Methods: Gastric mucosal damage was induced by intragastric administration of acidified ethanol in male Wistar rats. One hour later, gastric lesions were evaluated macroscopically. In gastro protection study, neurotensin was administered either intravenously (1.5, 3, and 5 µM/kg) or intracerebroventricularly (0.5, 1, and 2.5 nM/rat) 30 min before the ethanol challenge. In order to evaluate the involvement of central CB1 receptors in the gastro protective effect of neurotensin, the CB1 receptor antagonist AM251 (5, 10, and 15 nM/rat) was given i.c.v. 30 min prior to the administration of neurotensin. The effects of AM251 on the intact stomach and ethanol-induced gastric lesions were also evaluated. Results: Acidified ethanol induced large areas of gastric lesions which were significantly reduced by the highest dose of neurotensin in i.v. or i.c.v. application. The gastro protective effect of neurotensin was prevented by pretreatment with 15 nM/rat AM251. AM251 had no effect by itself. Conclusion: Peripherally or centrally given neurotensin protects gastric mucosa against damage induced by acidified ethanol through the activation of central cannabinoid CB1 receptors.

Objective (s): Targeting the neuropeptide systems has been shown to be useful for the development of more effective antipsychotic drugs. Neurotensin, an endogenous neuropeptide, appears to be involved in the mechanism of action of antipsychotics. However, the available data provide conflicting results and the mechanism (s) by which antipsychotics affect brain neurotensin neurotransmission have not been identified. Therefore, we aimed to investigate the effects of fluphenazine and amisulpride on brain regional contents of neurotensin considering the role of cannabinoid CB1 receptors which interact with neurotensin neurotransmission.Materials and Methods: Fluphenazine (0.5, 1, and 3 mg/kg) or amisulpride (3, 5, and 10 mg/kg) were administered intraperitoneally to male Wistar rats either for one day or 28 consecutive days. Twenty four hours after the last injection of drug or vehicle, neurotensin contents were determined in the mesocorticolimbic and nigrostriatal dopamine regions by radioimmunoassay. In the case of any significant change, the effect of pre-treatment with CB1 receptor antagonist, AM251 was investigated.Results: Chronic, but not acute, treatment with the highest dose of fluphenazine or amisulpride resulted in significant enhancement of neurotensin contents in the prefronatal cortex and nucleus accumbens. Fluphenazine also elevated neurotensin levels in the anterior and posterior caudate nuclei and substantia nigra. Neither amisulpride nor fluphenazine affected neurotensin contents in the amygdala or hippocampus. Pre-treatment with AM251 (3 mg/kg) prevented the neuroleptic-induced elevation of neurotensin. AM251 showed no effect by itself.Conclusion: The brain neurotensin under the regulatory action of CB1 receptors is involved in the effects of amisulpride and fluphenazine.

Introduction: Cannabinoid receptor type 1 (CB1) is extensively distributed across brain regions that are crucial for emotional processing, social cognition, and anxiety, including the prefrontal cortex, amygdala, and hippocampus. Dysregulation of CB1 receptors (CB1Rs) has been associated with several disorders characterized by impaired empathy, social behavior, and anxiety. Accordingly, this study investigates the modulatory role of CB1Rs in social interaction and anxiety in an empathic pain model in rats. Methods: A total of 48 adult male Wistar rats were used (n=8 for each group). One sibling received formalin injection into the hind paw five times within nine days (demonstrator), and the other siblings reported pain (observer) while being treated with dimethyl sulfoxide (DMSO), the CB1R agonist WIN 55,212–2 (WIN; 3 mg/kg, intraperitoneal), or the CB1R antagonist rimonabant (1 mg/kg intraperitoneal). Treatments were administered intraperitoneally 30 min before behavioral tests conducted on day 10, which were used to assess social behavior and anxiety.  Results: Empathic pain can impair social behavior and elicit anxiety-like effects. Rimonabant was effective in ameliorating deficits induced by empathic pain; conversely, WIN did not have a significant effect. Conclusion: CB1Rs play a modulatory role in social contagion. This modulation may provide new therapeutic targets for conditions, such as autism spectrum disorder, schizophrenia, and other psychological disorders characterized by impaired empathy and dysregulated social behavior associated with the CB1 signaling pathway.