Effect of testing conditions on the propsychotic action of MK-801 on prepulse inhibition, social behaviour and locomotor activity.
The present paper reports on two investigations designed with the aim of refining existing animal models representing several aspects of psychosis, used to evaluate antipsychotic potential of novel compounds. The aim of the first investigation was to determine the effect of habituating rats to the injection procedure on three behavioural testing paradigms, social interaction, locomotor activity and prepulse inhibition (PPI) of the acoustic startle response. Results showed that while there was no effect on social behaviour or locomotor activity, the habituating to injection procedure decreased startle magnitude. For the second study, the aim was to determine whether the order in which the tests were conducted would affect sensitivity to the effects of dizocilpine (MK-801), a non-competitive NMDA receptor antagonist known to induce social withdrawal, increase locomotor activity and disrupt PPI. Either social interaction or locomotor activity tests were carried out 3 days prior to PPI tests (protocol 1), or PPI tests were carried out 3 days prior to social interaction and locomotor activity tests (protocol 2). Results showed that protocol 2 rats were more sensitive to the social withdrawal-inducing, hyperlocomotive- and PPI-disruptive effects of MK-801. Based on these results, the testing conditions appear to have a significant influence on the outcome of experiments aimed at observing the propsychotic action of MK-801.
Gururajan
Anand
A
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, Victoria, Australia. anand.gururajan@pharm.monash.edu.au
Taylor
David Alan
DA
Malone
Daniel Thomas
DT
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D012919:Social Behavior; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate