Visual and auditory hallucinations11/21/2023 For a while, the other dopamine receptors, notably the D1 receptors, were suggested as other receptors possibly implicated in positive symptoms of schizophrenia, but it appeared that they were probably more involved in negative symptoms of schizophrenia, which consist of blunted effects and social withdrawal. This hypothesis has been reinforced by contemporaneous imaging techniques, which have confirmed that positive symptoms were associated with an increase of dopaminergic activity in the striatum. Consequently, the hypothesis that positive symptoms may be related to an excessive transmission of dopamine has become the main pharmacological model of positive symptoms in schizophrenia. It is these positive symptoms on which antipsychotic drugs have the most blatant therapeutic effects, and successive studies from the 1960's revealed that this effect could be due to antagonistic action on D2Rs, which is shared by all antipsychotic molecules. Schizophrenic hallucinations combined with other psychotic symptoms are commonly classified within the “positive symptoms” of schizophrenia. However, notable exceptions include early-onset forms in which visual and multisensory hallucinations are more frequent. Schizophrenic hallucinations are mainly auditory verbal. The Dopamine Model: Hallucinations, Antipsychotics, and Schizophrenia It is necessary to articulate these three mechanisms into an integrated model, or, alternatively, there may be different forms of hallucinations, that are mediated by different pharmacological supports and neurobiological circuits.Ģ.1. Initially, the existence of these different pharmacological systems underlying hallucinations appears incompatible with a unified conception hallucination. In schizophrenia, although antipsychotic blocking studies suggest that hallucinations result from D2R hyperstimulation, there are also numerous arguments for NMDAR dysfunction, which may be a potential and specific hallucinatory mechanism. Lastly, psychedelics act by stimulating the serotoninergic 5HT2A receptor (5HT2AR). Furthermore, “dissociative anesthetics” drugs induce complex schizophrenia-like clinical pictures, including hallucinations, that result from the blockade of glutamate NMDA receptors (NMDAR). Psychostimulants-induced hallucinations result from increased dopamine transmission and hyperactivation of dopamine D2 receptor (D2R). However, hallucinations may also be triggered by at least three different kinds of drugs: psychostimulants (i.e., cocaine or amphetamine), the so-called “dissociative anesthetics” (i.e., phencyclidine (PCP) or ketamine), and psychedelics, (i.e., lysergic diethylamid (LSD) and psilocybin).ĭepending on which situation is considered, the pharmacological hypotheses underlying the symptoms are completely different. While hallucinations may occasionally occur in diverse psychiatric and neurological pathologies, they are particularly characteristic of schizophrenia-related disorders, in which antipsychotic drugs are commonly used to treat them. We suggest that if there may be common neurobiological pathways between the different pharmacological systems that are responsible for the hallucinations, there may also be unique properties of each system, which explains the clinical differences observed.Ī hallucination is a type of misperception that can be defined as “the perception of an object without an object to perceive”. In addition, the nosological aspects of hallucinations and psychosis are addressed. In this review, such theories are discussed and faced with the clinical data. While some authors prefer one explanatory mechanism, others have proposed more integrated theories based on the different pharmacological psychosis models. A narrative review of the literature is proposed to synthesize how the main contributors in the field have approached and tried to solve these outstanding questions. Thus, we investigated whether the concept of hallucination is homogenous, both clinically and neurobiologically. Slight clinical differences are observed for each etiology. In schizophrenia, the relative importance of NMDAR and D2R in the occurrence of hallucinations is still debated. There are at least three different pharmacological ways to induce hallucinations: (1) activation of dopamine D2 receptors (D2Rs) with psychostimulants, (2) activation of serotonin 5HT2A receptors (HT2ARs) with psychedelics, and (3) blockage of glutamate NMDA receptors (NMDARs) with dissociative anesthetics. Hallucinations are complex misperceptions, that principally occur in schizophrenia or after intoxication induced by three main classes of drugs: psychostimulants, psychedelics, and dissociative anesthetics.
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