Abstract
A growing body of psychiatric research has emerged, focusing on the role of endocannabinoid system in psychiatric disorders. For example, the endocannabinoid system, via cannabinoid CB (CB1 and CB2) receptors, is able to control the function of many receptors, such as N-methyl-d-aspartate (NMDA) receptors connected strictly with psychosis or other schizophrenia-associated symptoms. The aim of the present research was to investigate the impact of the CB1 receptor ligands on the symptoms typical for schizophrenia. We provoked psychosis-like effects in mice by an acute administration of NMDA receptor antagonist, MK-801 (0.1–0.6 mg/kg). An acute administration of MK-801 induced psychotic symptoms, manifested in the increase in locomotor activity (hyperactivity), measured in actimeters, as well as the memory impairment, assessed in the passive avoidance task. We revealed that an acute injection of CB1 receptor agonist, oleamide (5–20 mg/kg), had no influence on the short- and long-term memory-related disturbances, as well as on the hyperlocomotion in mice, provoking by an acute MK-801. In turn, an amnestic effects or hyperactivity induced by an acute MK-801 was attenuated by an acute administration of AM 251 (0.25–3 mg/kg), a CB1 receptor antagonist. The present findings confirm that endocannabinoid system is able to modify a variety of schizophrenia-like responses, including the cognitive disturbances and hyperlocomotion in mice. Antipsychotic-like effects induced by CB1 receptor antagonist, obtained in our research, confirm the potential effect of CB1 receptor blockade and could have important therapeutic implications on clinical settings, in the future.
Highlights
Schizophrenia is a chronic, severe, mental disorder usually characterized by abnormal social behavior
As we mentioned in Introduction section, CB1 receptor agonists induced memory-related disturbances (Ferrari et al 1999; KrukSlomka and Biala 2016; Kruk-Slomka et al 2015a; Pamplona and Takahashi 2006), whereas antagonists of this type of receptors facilitated memory and learning processes in rodents evaluated in many memory tasks (Kruk-Slomka and Biala 2016; Kruk-Slomka et al 2015a; Lichtman 2000; Takahashi et al 2005; Terranova et al 1996)
CB1 receptor agonists were able to induce effects typical for schizophrenia; in turn, CB1 receptor antagonists had antipsychotic properties observed in rodents (Barzegar et al 2015; Kucerova et al 2014; Levin et al 2012; Roser and Haussleiter 2012)
Summary
Schizophrenia is a chronic, severe, mental disorder usually characterized by abnormal social behavior. It has been known that the function of different neurotransmitters systems, such as dopaminergic system, glutamatergic system, gamma-aminobutyric (GABA)-related system, or/and endocannabinoid system, is altered in psychosis (Broome et al 2005; Carlsson 2004). Glu is the major excitatory neurotransmitter in the brain which has a leading role in neural physiology, especially in mechanisms of synaptic plasticity, such as the long-term potentiation (LTP) and long-term depression underlying cellular basis of some phases of memory and learning (Riedel et al 2003; Shapiro 2001). Glutamatergic hypofunction, Neurotox Res (2016) 30:658–676 closely associated with NMDA receptors hypofunction, is currently believed to provoke dopaminergic deregulation observed in the brain of patients with schizophrenia (Harrison and Weinberger 2005; Javitt 2007) and underlie the symptoms recognized as schizophrenia (Mohn et al 1999; Stone et al 2007). Agonists of NMDA receptors may have the potential to attenuate the symptoms of schizophrenia, while antagonists of these receptors produce psychotic symptoms and others schizophrenia-associated symptoms (Abi-Saab et al 1998)
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