BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling “Negative-Like” Symptoms of Schizophrenia

Abstract

We attempted throughout the NO-system to achieve the particular counteraction of the ketamine-induced resembling “negative-like” schizophrenia symptoms in rats using pentadecapeptide BPC 157, and NO-agents, NG-nitro-L-arginine methylester (L-NAME), and/or L-arginine, triple application. This might be the find out the NO-system organized therapy (i.e., simultaneously implied NO-system blockade (L-NAME) vs. NO-system over-stimulation (L-arginine) vs. NO-system immobilization (L-NAME+L-arginine)). The ketamine regimen (intraperitoneally/kg) included: 3 mg (cognitive dysfunction, novel object recognition test), 30 mg (anxiogenic effect (open field test) and anhedonia (sucrose test)), and 8 mg/3 days (social withdrawal). Medication (mg/kg intraperitoneally) was L-NAME (5), L-arginine (100), and BPC 157 (0.01), alone and/or together, given immediately before ketamine (L-NAME, L-arginine, and combination) or given immediately after (BPC 157 and combinations). BPC 157 counteracted ketamine-cognition dysfunction, social withdrawal, and anhedonia, and exerted additional anxiolytic effect. L-NAME (antagonization, social withdrawal) and L-arginine (antagonization, cognitive dysfunction, anhedonia) both included worsening cognitive dysfunction, anhedonia, and anxiogenic effect (L-NAME), social withdrawal, and anxiogenic effect (L-arginine). Thus, ketamine-induced resembling “negative-like” schizophrenia symptoms were “L-NAME non-responsive, L-arginine responsive” (cognition dysfunction), “L-NAME responsive, L-arginine non-responsive” (social withdrawal), “L-NAME responsive, L-arginine responsive, opposite effect” (anhedonia) and “L-NAME responsive, L-arginine responsive, parallel effect” (both anxiogening). In cognition dysfunction, BPC 157 overwhelmed NO-agents effects. The mRNA expression studies in brain tissue evidenced considerable overlapping of gene overexpression in healthy rats treated with ketamine or BPC 157. With the BPC 157 therapy applied immediately after ketamine, the effect on Nos1, Nos2, Plcg1, Prkcg, and Ptgs2 (increased or decreased expression), appeared as a timely specific BPC 157 effect on ketamine-specific targets.

Stable Gastric Pentadecapeptide BPC 157 May Recover Brain–Gut Axis and Gut–Brain Axis Function

“…Thus, BPC 157 might act to favor the natural homeostasis of the GABA receptor complex as well as to enhance GABAergic transmission. In addition, there was an additional anxiolytic effect in the counteraction of negative schizophrenic symptoms in rats dosed with ketamine [ 103 ]. Importantly, these effects were shown to be related to the NO system effects as well [ 94 , 103 ].…”

“…In addition, there was an additional anxiolytic effect in the counteraction of negative schizophrenic symptoms in rats dosed with ketamine [ 103 ]. Importantly, these effects were shown to be related to the NO system effects as well [ 94 , 103 ].…”

Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Peptide Therapy in the Heart Disturbances, Myocardial Infarction, Heart Failure, Pulmonary Hypertension, Arrhythmias, and Thrombosis Presentation

“…Additionally, with BPC 157 therapy, there might be the brain–gut and gut–brain axis function recovery [ 2 , 193 ], while BPC 157, when given peripherally, might exert particular central beneficial effects [ 2 , 193 ]. Illustratively, these were the release of serotonin in the specific brain areas (i.e., nigrostriatum) [ 194 ], as opposed to the schizophrenia-like positive symptoms models [ 187 ] and schizophrenia-like negative symptoms models [ 195 ]. Finally, BPC 157 counteracted various encephalopathies [ 91 , 92 , 93 , 94 , 95 , 96 ].…”

Stable Gastric Pentadecapeptide BPC 157 and Striated, Smooth, and Heart Muscle

“…On the other hand, BPC 157 may counteract the opposite disturbances (i.e., stereotypies) that would appear in the course of the amphetamine, methamphetamine or apomorphine, or dopamine (over)-stimulation [ 26 , 52 , 53 ]. Note, these effects were assessed as counteractions of the positive-like symptoms and negative-like symptoms in the models of schizophrenia [ 26 , 27 ].…”

“…Conceptually, its practical significance has been ascribed to its particular role in the Selye’s stress response [ 3 , 7 , 8 ], as well as to its resolving of activities of the brain–gut and gut–brain axes [ 7 , 12 ]. Of note is the way that BPC 157 might counteract various encephalopathies [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], behavioral disturbances [ 22 , 23 , 24 , 25 , 26 , 27 ] (particularly those representing psychiatric illness models [ 25 , 26 , 27 ]) and CNS disturbance-induced muscle disabilities [ 19 , 20 , 21 , 22 , 25 , 28 , 29 , 30 , 31 ], in particular. However, the findings that the stable gastric pentadecapeptide BPC 157 might beneficially affect striated and smooth muscle and heart might suggest that it most perfectly matched [ 32 , 33 , 34 ] with the original Robert’s and Szabo’s cytoprotective theory and concept [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”