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.
SCROLL
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
IN VIVO 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) |
| 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
IN VIVO MODELS
| Brain slices (LTP) | Rat |
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
IN VIVO 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 |
| 6Hz psychomotor | Mouse – Rat – Gerbil |
| Audiogenic seizures | Mouse |
| 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
IN VIVO MODELS
IN VIVO 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 |
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) |
| 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
IN VIVO 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 |
| 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 |
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