Animal models of serotonergic psychedelics.

The serotonin 5-HT(2A) receptor is the major target of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Serotonergic psychedelics induce profound effects on cognition, emotion, and sensory processing that often seem uniquely human. This raises questions about the validity of animal models of psychedelic drug action.

Clozapine-induced locomotor suppression is mediated by 5-HT2A receptors in the forebrain.

The need for safer, more effective therapeutics for the treatment of schizophrenia is widely acknowledged. To optimally target novel pharmacotherapies, in addition to establishing the mechanisms responsible for the beneficial effects of antipsychotics, the pathways underlying the most severe side effects must also be elucidated. Here we investigate the role of serotonin 2A (5-HT(2A)), serotonin 2C (5-HT(2C)), and dopamine 2 receptors (D₂) in mediating adverse effects associated with canonical first- and second-generation antipsychotic drugs in mice.