The aim of this study was to systematically and in detail investigate the effects of stable pentadecapeptide BPC 157 in interaction with NO-compounds in models of psychosis and antipsychotic side effects in rats. A total of 558 male Wistar rats were used. In the group of acute experiments, a total of 378 rats were used and the agents were administered once. A total of 180 rats were used in chronic experiments. The trials were divided into acute (motor hyperactivity, catalepsy, memory deficits, negative symptoms, and glucose intolerance) and subchronic trials (social interaction, locomotor sensitization). In such suitable models, we focused on the ratio of the effect of BPC 157, L-NAME (NOS inhibitor) and L-arginine (NOS substrate) to psychosis-like symptoms, which were induced by different agents in doses that induced the desired behavior. Agents (mg / kg intraperitoneally, i.p.) L-NAME (5.0), L-arginine (100.0), BPC 157 (0.01), were administered alone and / or together, 5 minutes before the onset of acute motor impairment (indirect / direct dopamine agonists (amphetamine (3.0), apomorphine (2.5)), noncompetitive NMDA receptor antagonist (MK-801 (0.2)), catalepsy (dopamine receptor antagonist haloperidol (2.0)) , cognitive impairment (non - competitive NMDA receptor antagonist (ketamine (3.0)), anxiety and anhedonia (non - competitive NMDA receptor antagonist (ketamine (30.0)). In a social interaction model, a noncompetitive NMDA receptor antagonist (ketamine (8.0)) was administered over 3 days. Alternatively, BPC 157 (0.01) was administered immediately after L-NAME (40 mg / kg) i.p. Also, BPC 157 was administered immediately before bolus glucose (glucose (1.0)) and the antipsychotic olanzapine (olanzapine (15,0)) and 60 minutes after olanzapine. To induce or prevent sensitization, we used chronic administration of methamphetamine in increasing doses, alternately 3 days during the first 3 weeks (methamphetamine) (3.0 - 6.0 - 9.0), and challenge after the next 4 weeks (methamphetamine (0.5) and medications (L-NAME, L-arginine, BPC 157) 5 minutes before methamphetamine in the second and third weeks. Given alone, BPC 157 or L-arginine suppressed the effects induced by amphetamine, apomorphine, and MK-801 in neurochemical models of psychosis, haloperidol-induced catalepsy, ketamine-induced spatial memory imapairment, ketamine-induced anxiety (only BPC 157) and anhedonia, and chronic methamphetamine induced sensitisation. BPC 157 reduced the ketamine-induced social deficit, while L-arginine nullified the beneficial effect of L-NAME in that test. L-NAME did not affect the effects caused by apomorphine and MK-801, catalepsy caused by haloperidol, chronic sensitization caused by methamphetamine, spatial memory deficit caused by ketamine, worsened anhedonia, but also suppressed the acute effect of amphetamine and social deficit induced by ketamine. In combinations (L-NAME + Larginine), specific for NO, L-NAME counteracts L-arginine-induced antagonism in apomorphine-, MK-801-, haloperidol-, methamphetamine- and ketamine rats, but not in amphetamine- rats. Unlike L-arginine, BPC 157 maintains its counter-effect in the presence of NOS blockade (L-NAME + BPC157) or overstimulation of the NO system (L-arginine + BPC157). Illustrating the relationships of BPC 157-L-arginine, BPC 157 restored the antagonism (L-NAME + L-arginine + BPC157) which was abolished by co-administration of L-NAME with L-arginine (L-NAME + L-arginine). BPC 157 directly inhibited high-dose LNAME- induced catalepsy. Finally, BPC 157 suppressed bolus glucose-induced hyperglycemia and olanzapine-induced hyperglycemia and catalepsy. Based on the obtained results, it can be concluded that there are two characteristic presentations of NO-pathways: antagonism (opposite effects) or synergism (parallel effects), where the effect of BPC 157 is always superior. The present study provides experimental evidence that the pentadecapeptide BPC 157 is effective in suppressing behavioral effects associated with stimulation or blockade of dopamine receptors, blockade of NMDA receptors, or blockade of the NO system suggesting a functional interaction between this peptide and the dopaminergic / glutamatergic / nitrergic system. BPC 157 has a special modulating effect, required to maintain the proper functioning of several neurotransmitter systems. BPC 157 has a particularly safe profile, which is quite different from standard pharmacological agents. In fact, unlike neuroleptics and antidepressants, BPC 157 has particular cardioprotective and antiarrhythmic effects, and now shown also antidiabetogenic effect. Based on the validity of the animal models used, it can be concluded that BPC 157 could play a significant role in the regulation of positive and negative symptoms, and cognitive impairment in schizophrenia.