RenaSci

Other Behavioural Assays

Behavioural and Physiological Assays

 

We offer a wide range of other behavioural and physiological assays which can be used to assess the mode of action, efficacy or side-effect profile of centrally-acting drugs or used for proof of concept studies for novel molecular targets in the brain. These assays include :-

 

     •     Behavioural phenotyping (transgenic animals)

     •     Initial safety assessment of novel compounds
                 -     Irwin test
                 -     Rotarod (rats and mice)

     •     Neurotransmitter-specific functional tests

     •     Measurement of the effects of drugs on seizure threshold

 

Drugs (alone or in combination with a receptor agonist or antagonist) can be given by a variety of different routes (including non-surgical intracerebroventricular injection). Blood and tissue samples can be collected for pharmacokinetic or neurochemical analysis or ex vivo binding if required.

 

Neurotransmitter-specific functional tests

 

Some examples of simple functional tests which can be used to characterise novel drugs in vivo include :-

     •     Reversal of clonidine-induced hypoactivity and mydriasis in rats and mice
           (mediated by activation of central presynaptic α2A- and postsynaptic
           α2A-adrenoceptors, respectively). These assays can be used as functional tests for
           α2A-adrenoceptor antagonists

Clonodine-induced Mydriasis in Mice

     •     Reversal of the catalepsy induced by the D2-receptor antagonist, haloperidol,
           in rats and mice (eg attenuation of haloperidol-induced catalepsy in rats can be used
           to detect novel adensoine A2A receptor antagonists with in vivo efficacy or as a 
           rapid screen for compounds with antiparkinsonian activity)

Reversal of Haloperidol-induced Catalepsy

 

     •     Reversal of 8-OHDPAT-induced hypothermia in mice which can be used to screen
           for  5-HT1A receptor antagonists

 

Measurement of the effects of drugs on seizure threshold

 

Proconvulsant (or anticonvulsant) activity of a test compound can be assessed using a number of different pre-clinical models. These include determining its ability to modulate the seizures induced by intravenous (iv) administration of the non-competitive GABA antagonist, pentylenetetrazole (PTZ).  In the model, mice receive an infusion of PTZ (15 mg/kg at a rate of 0.2 ml/min) via the tail vein and the time until clonic and tonic seizures emerge is recorded. This enables the dose of PTZ producing seizures to be accurately measured. Drugs with proconvulsant activity will reduce the dose of PTZ required to produce seizures. Drugs with anticonvulsant activity will impair the action of PTZ and increase the dose required to induce seizures. The timed iv PTZ infusion test can therefore be used to screen for adverse side-effects (potential proconvulsant activity) or as a screen for putative anticonvulsants.


We have recently validated the timed iv PTZ infusion model using the non-selective benzodiazepine partial inverse agonist, FG-7142, which significantly reduced the dose of PTZ required to produce clonic and tonic seizures in mice.

Effect of FG-7142 on PTZ-induced Seizures

Consistent with the literature, MRK-016, a α5-subtype selective GABAA receptor inverse agonist, was not proconvulsant in the timed iv PTZ infusion test.

Effect of MRK-016 on PTZ-induced Seizures

 

Please contact us for further information about our existing animal models or for novel assay development.

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