Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia

Abstract

Schizophrenia is a serious neuropsychiatric disorder characterized by the presence of positive symptoms (hallucinations, delusions, and disorganization of thought and language), negative symptoms (abulia, alogia, and affective flattening), and cognitive impairment (attention deficit, impaired declarative memory, and deficits in social cognition). Dopaminergic hyperactivity seems to explain the positive symptoms, but it does not completely clarify the appearance of negative and cognitive clinical manifestations. Preclinical data have demonstrated that acute and subchronic treatment with NMDA receptor antagonists such as ketamine (KET) represents a useful model that resembles the schizophrenia symptomatology, including cognitive impairment. This latter has been explained as a hypofunction of NMDA receptors located on the GABA parvalbumin-positive interneurons (near to the cortical pyramidal cells), thus generating an imbalance between the inhibitory and excitatory activity in the corticomesolimbic circuits. The use of behavioral models to explore alterations in different domains of memory is vital to learn more about the neurobiological changes that underlie schizophrenia. Thus, to better understand the neurophysiological mechanisms involved in cognitive impairment related to schizophrenia, the purpose of this review is to analyze the most recent findings regarding the effect of KET administration on these processes.

The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity

“…This observation substantiated the glutamate hypothesis and glutaminergic dysfunction as a mechanism underlying both positive and negative symptoms, as well as cognitive dysfunction, in schizophrenia [ 194 ]. Thereby, ketamine as the model of schizophrenia in rats [ 193 ] (as acute ketamine administration was associated with schizophrenia-like or psychotomimetic symptoms with large effect sizes and an increase in positive and negative symptoms [ 195 , 196 ]) might escape from the extraordinary complexity of extrapolation from animal models of mental disorders in general [ 197 , 198 , 199 ].…”

Ketamine modulates disrupted in schizophrenia-1/glycogen synthase kinase-3β interaction

“…These developmental changes are consistent with synaptic pathology seen in laboratory models of both anesthetic-induced neurotoxicity and schizophrenia. This association between NMDAR dysfunction and psychiatric conditions has been established in several laboratory animal and human studies ( Snyder and Gao, 2013 ) and ketamine has been utilized for investigating schizophrenia and mood disorders in preclinical and clinical settings ( Suárez Santiago et al, 2023 ).…”

Rethinking Mental Automatism: De Clérambault’s Theory in the Age of Novel Psychoactive Drugs: Psychotropic Effects and Synthetic Psychosis

“…Several experimental studies have since corroborated this notion, demonstrating drug effects that mirror both the positive symptoms (e.g., hallucinations, delusions, paranoia, and disorganized thinking) and negative symptoms (e.g., affective flattening, anhedonia, attentional and cognitive impairment) characteristic of schizophrenia [ 38 , 39 , 40 ]. Current major neurobiological theories of schizophrenia trace their roots back to the effects of various substances: the serotonergic model stemmed from observations of lysergic acid diethylamide (LSD) [ 41 ], the dopamine hypothesis emerged from studies on amphetamines, and the glutamatergic model was influenced by research on phencyclidine (PCP) and ketamine [ 42 , 43 , 44 , 45 , 46 ]. More recently, interest has grown in the role of endocannabinoids, spurred by the effects of cannabis [ 47 , 48 , 49 ].…”