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In humans, diurnal tooth-clenching and other oral stereotyped behaviour are associated with stress/anxiety. In rodents, gnawing/biting of objects is observed during exposure to stress. Both nigrostriatal and mesocortical dopaminergic systems are involved in the development of this coping behaviour. To clarify the relationship between central dopaminergic activity and stress-induced parafunctional masticatory behaviour, using microdialysis in vivo, we assessed the changes in extracellular dopamine concentrations in both prefrontal cortex and striatum of rats subjected to a mild tail pinch. The animals were divided into two groups according to the degree of non-functional masticatory activity (NFMA) displayed during exposure to tail pinch. In prefrontal cortex, rats which displayed severe NFMA showed a greater increase in extracellular dopamine concentration in relation to basal values (Emax=184±26%) than those which did not display this coping behaviour (Emax=139± 23%) (F(NFMA) [1,86]=3·97; P<0·05) (n=17). A positive association was also found between cortical dopamine maximal value from baseline and the degree of NFMA displayed (r=0·36; P<0·05) (n=17). There were no significant differences in the tail-pinch-induced striatal dopamine increase between both groups of rats (Emax=130±10%) (n=17). These results provide further evidence in support of prefrontal dopamine playing a relevant role in the expression of stress-induced masticatory coping behaviour.

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Cannabis use disorder is frequent in schizophrenia patients, and it is associated with an earlier age of onset and poor schizophrenia prognosis. Serotonin 2A receptors (5‐HT2AR) have been involved in psychosis and, like Akt kinase, are known to be modulated by THC. Likewise, endocannabinoid system dysregulation has been suggested in schizophrenia. The presence of these molecules in blood makes them interesting targets, as they can be evaluated in patients by a minimally invasive technique. The aim of the present study was to evaluate 5‐HT2AR protein expression and the Akt functional status in platelet homogenates of subjects diagnosed with schizophrenia, cannabis use disorder, or both conditions, compared with age‐ and sex‐matched control subjects. Additionally, endocannabinoids and pro‐inflammatory interleukin‐6 (IL‐6) levels were also measured in the plasma of these subjects. Results showed that both platelet 5‐HT2AR and the active phospho (Ser473)Akt protein expression were significantly increased in schizophrenia subjects, whereas patients with a dual diagnosis of schizophrenia and cannabis use disorder did not show significant changes. Similarly, plasma concentrations of anandamide and other lipid mediators such as PEA and DEA, as well as the pro‐inflammatory IL‐6, were significantly increased in schizophrenia, but not in dual subjects. Results demonstrate that schizophrenia subjects show different circulating markers pattern depending on the associated diagnosis of cannabis use disorder, supporting the hypothesis that there could be different underlying mechanisms that may explain clinical differences among these groups. Moreover, they provide the first preliminary evidence of peripherally measurable molecules of interest for bigger prospective studies in these subpopulations.