Mood disorders and Psychosis

CENTRAL NERVOUS SYSTEM

Porsolt offers models in all areas of psychopharmacology, epilepsy, sleep-wake, and neurodegenerative disorders. We are uniquely placed to offer a full range of CNS efficacy and safety pharmacology assessments, from basic models and regulatory tests, through the evaluation of abuse and dependence liability and proconvulsant risk using EEG.

Mood disorders and Psychosis

Porsolt has a considerable expertise with Psychopharmacology to target psychoactive properties of drug candidate. Starting from basic psychopharmacology screening, we offer to evaluate new compounds in advanced studies of depression, anxiety and psychosis.

Expert in behavioral testing, we provide tailored models and develop new study designs adapted to your needs, do not hesitate to contact us !

DEPRESSION AND ANXIETY STUDIES

Although depression and anxiety are generally considered as distinct disorders, they share common causes or neurobiological mechanisms. Anxiolytics are generally not active against depression, while many antidepressants are active after chronic treatment against some anxiety disorders. At Porsolt, we offer testing procedures relevant for the detection of antidepressant or anxiolytic-like activity alone, and procedures that can be useful for both indications.

Screening for antidepressant-like activity

We perform the recognized method developped by Roger Porsolt for  the detection of antidepressant activity: Behavioral Despair Test known as Porsolt Test (Porsolt et al - Arch. Int. Pharmacodyn., 229, 327-336, 1977). Forced to swim in a situation from which they cannot escape, rodents become rapidly immobile. Antidepressants decrease the duration of immobility, anxiolytics are inactive in this test.

Mixed anxiolytic/antidepressant-like activity

Although marble burying behavior in mice is considered as a test for anxiety disorders, this simple test is sensitive to various classes of both antidepressant and anxiolytic agents currently used in the clinic: Benzodiazepines (e.g. clobazam), SSRIs (e.g. fluoxetine) or 5-HT1A compounds (e.g. buspirone). Effects in this test should be confirmed in follow-up studies.

Studies predictive of antidepressant efficacy

Porsolt provides multiple tests to validate the antidepressant properties of new  drug candidate:

• Tolerance/Rate of onset can be evaluated by the Open Space Swimming Test (OSST)

• Treatment-resistant depression or mixed anxiety/depressive-like state can be evaluated by Chronic corticosterone (cort) in collaboration with Prof. Denis David (University of Paris Sud) or Chronic Mild Stress (CMS) models

• Differential Reinforcement of Low rate (DRL30) test detects anti-impulsive effects of antidepressants

Studies predictive of anxiolytic activity

These tests are designed to assess anxiolytic efficacy:

• Punishment-induced Conflict: Vogel conflict / 4 Plates test / Fear Potentiated Startle (FPS)

• Anticipatory anxiety: Stress-induced hyperthermia

• Natural aversion: Elevated plus maze /Light-dark box /Marble burying /Emotional hypophagia

Porsolt also provides solutions to evaluate the effects of substances on

• Social anxiety, Autonomic effects and Conditionned fear.

PSYCHOSIS STUDIES

Advanced Studies of antipsychosis activity

Porsolt offer to evaluate antipsychotic properties of new compounds by caracterize their mechanism of action in several models of induced deficits or symptoms.

Positive symptoms:

Hyperactivity induced by Amphetamine, Apomorphine, MK-801, PCP
Amphetamine-induced stereotypies
Apomorphine-induced climbing

Negative symptoms:

Social interaction deficits - acute MK-801, in development

Cognitive deficits

Deficits induced by MK-801 or PCP are evaluated in behavioral studies:  Morris water maze, Social recognition, Passive avoidance, Delayed alternation and Operant reversal

Sensory filtering – pre-attentional processes

Disruption of pre-pulse inhibition (PPI) by apomorphine, MK-801 or PCP (in development)

Side effect liability of antipsychotics

We evaluate the induction of Catalepsy during an antipsychotic treatment.

We investigate the Effects on glucose metabolism by testing Glucose tolerance tests (Oral glucose tolerance test (OGTT) and Intravenous glucose tolerance test (IVGTT) and body weight gain. Key metabolic biomarkers assays could be an additional insight for evaluate side effects.