BPC 157, L-NAME, L-Arginine, NO-Relation, in the Suited Rat Ketamine Models Resembling “Negative-Like” Symptoms of Schizophrenia
Andrea Zemba Čilić, M. Zemba, M. Cilic, S. Štrbe, Spomenko Ilić, J. Vukojević, Z. Zoričić, I. Filipčić, A. Kokot, I. M. Smoday, Iva Rukavina, A. Boban Blagaić, A. Tvrdeić, Božidar Duplancic, V. Stambolija, D. Marcinko, A. Škrtić, S. Seiwerth, P. Sikiric
Biomedicines June 21, 2022 DOI: 10.3390/biomedicines10071462 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | BPC 157 L-NAME L-arginine ketamine |
| Dose | ketamine: 3 mg, 30 mg, 8 mg/3 days; L-NAME: 5 mg; L-arginine: 100 mg; BPC 157: 0.01 mg (all mg/kg intraperitoneally) |
| Topics | Esketamine Ketamine |
| Key points | BPC 157 counteracted ketamine-induced cognitive dysfunction, social withdrawal, and anhedonia, and exerted an additional anxiolytic effect in rats. |
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
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- Effects of nitric oxide-related compounds in the acute ketamine animal model of schizophrenia BMC Neuroscience March 5, 2015
- Role of nitric oxide in experimental models of psychosis in rats. Methods and findings in experimental and clinical pharmacology November 1, 2001