Animal models for predicting the efficacy and side effects of antipsychotic drugs

Abstract

The use of antipsychotic drugs represents an important approach for the treatment of schizophrenia. However, their efficacy is limited to certain symptoms of this disorder, and they induce serious side effects. As a result, there is a strong demand for the development of new drugs, which depends on reliable animal models for pharmacological characterization. The present review discusses the face, construct, and predictive validity of classical animal models for studying the efficacy and side effects of compounds for the treatment of schizophrenia. These models are based on the properties of antipsychotics to impair the conditioned avoidance response and reverse certain behavioral changes induced by psychotomimetic drugs, such as stereotypies, hyperlocomotion, and deficit in prepulse inhibition of the startle response. Other tests, which are not specific to schizophrenia, may predict drug effects on negative and cognitive symptoms, such as deficits in social interaction and memory impairment. Regarding motor side effects, the catalepsy test predicts the liability of a drug to induce Parkinson-like syndrome, whereas vacuous chewing movements predict the liability to induce dyskinesia after chronic treatment. Despite certain limitations, these models may contribute to the development of more safe and efficacious antipsychotic drugs.

Synthesis, docking studies, and pharmacological evaluation of 5HT2C ligands containing the N′‐cyanoisonicotinamidine or N′‐cyanopicolinamidine nucleus

“…Taking into account that selective 5‐HT 2C ligands may have the therapeutic potential for the treatment of schizophrenia in humans, in the second stage of our research, we intended to evaluate the antipsychotic ability of the new compounds. The preclinical studies utilize mainly the amphetamine model to estimate antipsychotic properties of drugs . As it is based on manipulation of the dopaminergic pathways, it may primarily respond to drugs that affect this neurotransmitter system and many neuroleptics acting as dopaminergic antagonists reverse this effect .…”

Effects of β-Arrestin-Biased Dopamine D2 Receptor Ligands on Schizophrenia-Like Behavior in Hypoglutamatergic Mice

“…In addition, rodents given NMDA antagonists display social withdrawal that can be partially rescued with certain APDs (Geyer and Ellenbroek, 2003;Porsolt et al, 2010;Gobira et al, 2013). In the sociability test, vehicle-treated NR1 WT mice demonstrated high social affiliation and social preference for the novel mouse, whereas NR1-KD animals showed no preferences in either test.…”

The Krushinsky-Molodkina rat strain: The study of audiogenic epilepsy for 65 years

“…Apart from well-described neuroleptic catalepsy (induced by several groups of drugs) [28], at least three laboratory catalepsy models were suggested, in which the "natural" cataleptic state could be analyzed. They were as follows: spontaneous catalepsy [29], a "pinch"-induced catalepsy which developed in response to pinch (forced press of the nape skin by fingers) [30]; postictal catalepsy [31]; and audiogenic postictal catalepsy (Fig.…”