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, to the evaluation of abuse and dependence liability and proconvulsant risk using EEG.

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Central Nervous System

CENTRAL NERVOUS SYSTEM DISEASE

CNS General Screening

CNS General Screening is an investigative tool assessing the involvement of the central nervous system (CNS).

IN VITRO MODELS
Calcium response (release or sponsaneous oscillation) Mouse - Rat primary neurons
Cytolysis / Viability Mouse - Rat primary neurons
Mitochondrial membrane potential measurement Mouse - Rat primary neurons
Neurotoxicity profiling (calcium spontaneous oscillation modulation) hiPSC mixed culture organoid (Astrocytes and Neurons)
IN VIVO MODELS
Accelerating rotarod Mouse – Rat
Activity meter Mouse – Rat
Barbiturate interaction (sleep induction) Mouse – Rat
Beam walking Mouse – Rat
Ethanol interaction (sleep induction) Mouse – Rat
Foot-fault Rat
Grip strength Mouse – Rat
Neurological score Rat
Odor discrimination Rat
Primary observation (Irwin) Mouse – Rat
Rectal temperature (option: implants) Mouse – Rat
Removal of adhesive Rat
Rotarod Mouse – Rat
Tetrad test Mouse – Rat

Cognition & Aging

Enhancement and decline of cognitive ability is measured, including the effects of aging.

IN VIVO MODELS

AGE-RELATED DEFICIT

Delayed alternation (acquisition) Aged Rat
Delayed alternation (stabilized performance) Aged Rat
Morris water maze (acquisition and retention) Aged Mouse – Aged Rat
Operant reversal Aged Rat
Social recognition Aged Rat
Y Maze - Spontaneous alternation Aged Mouse – Aged Rat

EXPERIMENTAL PROCEDURES

Delayed alternation (acquisition) Rat
Delayed alternation (stabilized performance) Rat
Fear Conditioning (context) Mouse – Rat
Fear Conditioning (cue & extinction) Mouse
Morris water maze (single session) Rat
Morris water maze (acquisition and retention) Mouse – Rat
Operant reversal Rat
Operant Set-shifting Rat
Passive avoidance Mouse – Rat
Social recognition (30 minute retention) Rat
Social recognition (120 minute retention(delay-induced forgetting)) Rat
Y-Maze - Spontaneous Alternation Mouse – Rat

MODELS OF PHARMACOLOGICALLY - INDUCED AMNESIA

Diazepam - induced amnesia

Passive avoidance Mouse - Rat

MK 801 - induced amnesia

Delayed alternation (stabilized performance) Rat
Morris water maze (acquisition and retention) Rat
Operant reversal Rat
Passive avoidance Rat
Social recognition (30 minute retention) Rat

PCP - induced amnesia

Delayed alternation (stabilized performance) Rat
Operant reversal Rat

Scopolamine - induced amnesia

Delayed alternation (stabilized performance) Rat
Morris water maze (acquisition and retention) Rat
Morris water maze (single session) Rat
Operant reversal Rat
Passive avoidance Mouse - Rat
Social recognition (30 minute retention) Rat

Drug Abuse & Dependence

Abuse is the desire to take drugs for non-medical purposes whereas Dependence is the need for the drug because of withdrawal symptoms.

IN VIVO MODELS
Drug discrimination Rat
Flumazenil-precipitated withdrawal (ECS threshold) Mouse
Naloxone-precipitated withdrawal (Saelens) safety-efficacy Mouse – Rat
Non-precipitated withdrawal (option: telemetry) Rat
Opiate tolerance (hot plate) Mouse - Rat
Place preference Mouse - Rat
Self-administration (initiation) Rat
Self-administration (substitution) Rat
Self-administration (reinstatement) Rat
Self-administration (progressive ratio) Rat
Validation of diazepam in drug discrimination Rat

Electrophysiology

Electrical recording techniques used in biological tissues, that enable the measurement of ion currents.

EX-VIVO MODELS
Brain slices (LTP) Rat
IN VIVO MODELS

CONCIOUS ANIMALS (TELEMETRY)

EEG trace monitoring Mouse – Rat – Dog
Electrical amygdala kindling Rat
Quantified EEG Mouse – Rat - Dog
Sleep/wakefulness cycle Rat

Epilepsy

Epilepsy is a disorder in which brain activity becomes abnormal, causing seizures or periods of unusual behaviors and sensations.

IN VITRO MODELS
4-AP calcium spontaneous oscillation modeulation Mouse - Rat Primary Neurons
GABA Pathway (calcium spontaneous oscillations) Mouse - Rat Primary Neurons, and hiPSC mixed culture organoid
Glutamate pathway (calcium release and spontaneous oscillations) Mouse - Rat Primary Neurons, and hiPSC mixed culture organoid
Kainate (calcium release) Mouse - Rat Primary Neurons, and hiPSC mixed culture organoid
NMDA antagonists (calcium release) Mouse - Rat Primary Neurons
IN VIVO MODELS
6Hz psychomotor Mouse – Rat – Gerbil
Audiogenic seizures Rat
Bicuculline convulsions Mouse – Rat
Electrical amygdala kindling (Electrophysiology) Rat
Electroconvulsive threshold Mouse – Rat – Gerbil
GBL-induced absence epilepsy (EEG telemetry) Mouse
Intravenous PTZ seizure threshold Rat
Kainic acid convulsions Rat
Kainic acid induced spontaneous seizure Rat
Maximal electroshock Mouse – Rat
Pentylenetetrazole seizures Mouse – Rat – Dog
Pilocarpine induced spontaneous seizure Rat
Picrotoxin convulsions Mouse – Rat
Strychnine convulsions Mouse – Rat

Neurodegeneration

Neurodegeneration refers to the progressive atrophy and loss of function of neurons, present in neurodegenerative diseases.

IN VITRO MODELS
Glutamate-induced excitotoxicity Rat cortical or hippocampal neurons
Immune cell phagocytosis (E.Coli particles) hiPSC derived microglia
Immune cell phagocytosis (S.Aureus particles) hiPSC derived microglia
Inflammatory cytokine release (LPS stimuli) hiPSC derived microglia
IN VIVO MODELS

ALZHEIMER DISEASE

Streptozotocin (STZ) – induced cognitive deficit Rat
Experimental Procedures
 Morris water maze
 Delayed alternation

HUNTINGTON DISEASE

Motor function and neuroscore subchronic 3-NPA Rat
Experimental Procedures
 Activity meter
 Rotarod
 Lesion volume

PARKINSON DISEASE

IN VITRO MODELS
6-OHDA/(Cytolysis / Viability) SH-SY5Y cells
6-OHDA/induced toxicity (Neurite outgrowth of dopamine neurons) hiPSC derived dopaminergic neuron
MPP + induced toxicity (Neurite outgrowth and cytolysis) hiPSC derived dopaminergic neuron
MPP+ induced toxicity in 3D (calcium spontaneous oscillation modulation) hiPSC mixed culture organoid(Astrocytes and Neurons)
Rotenone induced toxicity (Cytolysis / Viability) SH-SY5Y cells
Rotenone induced toxicity (Neurite outgrowth of dopamine neurons) hiPSC derived dopaminergic neuron
Rotenone induced toxicity in 3D (calcium spontaneous oscillation modulation) hiPSC mixed culture organoid (Astrocytes and Neurons)
IN VIVO MODELS
Alpha Synuclein PFF model Mouse
Cognitive deficit Bilateral striatal 6-OHDA lesion Rat
L-DOPA dyskinesia Unilateral medial forebrain bundle (mfb) 6-OHDA lesion Rat
Psychosis-like-behaviour Bilateral striatal 6-OHDA lesion Rat
Stepping behavior unilateral medial forebrain bundle (mfb) 6-OHDA lesion Rat
Tremor Tacrine-induced Tremulous Jaw-Movements (TJM) Rat
Turning behavior Unilateral medial forebrain bundle (mfb) 6-OHDA lesion Rat

Psychiatric Diseases

Psychiatric diseases are disorders that greatly disturb thinking, moods, and behavior.

IN VIVO MODELS

ANXIETY

Elevated plus-maze Mouse – Rat – Gerbil
Fear potentiated startle reflex Rat
Four plates Mouse
Light-dark box Mouse
Marble burying Mouse
Novelty-induced hypophagia Mouse - Rat
Staircase Mouse
Stress-induced hyperthermia (group-housed animals) Mouse
Stress-induced hyperthermia (singly-housed animals) (option: implants) Mouse
Vogel conflict Rat

DEPRESSION

Behavioral despair Mouse – Rat
Chronic Mild Stress Mouse
Differential Reinforcement of Low rate (DRL 30) Rat
Open space swimming Mouse

PSYCHOSIS

Amphetamine hyperactivity Mouse – Rat
Amphetamine stereotypy Mouse - Rat
Apomorphine climbing Mouse
Catalepsy Mouse - Rat
Dual-hit neonatal PCP and post-weaning social isolation Rat
Low dose apomorphine Mouse
Mescaline scratching Mouse
MK-801 hyperactivity Mouse - Rat
Obsessive Compulsive Disorder (OCD)/8OHDPAT Rat
PCP hyperactivity Mouse - Rat
Prepulse inhibition (deficit induced by apomorphine) Rat
Prepulse inhibition (deficit induced by MK-801) Rat
Prepulse inhibition (deficit induced by PCP) Rat
Sociability (3-Chamber) Test Mouse
Social investigation (deficit induced by MK-801) Rat

Stroke

Stroke occurs when the blood supply to part of the brain is interrupted or reduced, preventing brain tissue from receiving oxygen and nutrients.

IN VITRO MODELS
Excitatory neurotransmitter induced excitotoxicity (Cytolysis)(Glutamate, NMDA, and Kainate Mouse - Rat Primary Neurons
Excitatory neurotransmitter induced excitotoxicity (Mitochondrial Membrane Potential) (Glutamate, NMDA, and Kainate) Rat / Mouse primary neurons
Excitatory neurotransmitter induced excitotoxicity (Calcium Response) (Glutamate, NMDA, and Kainate) Rat / Mouse primary neurons
IN VIVO MODELS
Intrastriatal NMDA administration Mouse
Experimental Procedures
 Lesion volume
Ransient Focal Cerebral Ischemia Middle Cerebral Artery Occlusion Rat
Experimental Procedures
 Beamwalking
 Foot-Fault
 Removal of Adhesive
 Neurological Score
 Lesion Volume
BIOMARKER ASSAYS
PLATFORM BIOMARKER SPECIES (SAMPLE)
Histology (IHC-P) Neurons (pan neuron, dopaminergicGABA interneuron, Purkinje) Rat - Mouse - Pig
Glial cells (astrocytes, microglia, oligodendrocytes Rat - Mouse - Pig
Aggregated protein α-synuclein Human-Mouse (cell supernatant and brain)
Neuron activity proteins(synapse, myelination) Rat - Mouse
Nerve growth factor (NPY, TrkA) Rat - Mouse
Staining (paraffin slices) Hematoxylin & Eosin, Sirius red, Masson’s trichrome,… Multiple species & tissues
CBA Inflammation pathway IL-6, IL-10, MCP-1or IL-8 IFN-γ or IL-1β ,TNF and IL-12p70 Human - Mouse (cell supernatant)
ELISA RAS/Erk Signaling (Erk, P-Erk, S6, P-S6) Mouse (Pancreas, cerebellum)
Alzheimer Pathway(P-Tau Ser398, P-Tau Ser202 Tyr205, GSK3b & P-GSK3) Rat (Hippocampus)
Amyloid proteins (β-amyloid) Dog (CSF, plasma)
CBA - ELISA - WB - IHC-PIHC-Fr - ICC - HTRF Other targets upon request Multiple species & biological specimens

Porsolt

Z.A. de Glatigné
53940 Le Genest-Saint-Isle, France
Telephone +33 2 43 69 36 07

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