Dissociation between MK-801- and captivity-induced stereotypies in bank voles.

Abstract

Pharmacologically induced stereotypies (PHIS) following dopamine agonists and, more recently, the non-competitive NMDA antagonist dizocilpine (MK-801), are used to study human psychopathology and for screening potential neuroleptic drugs. On the other hand, bank voles (Clethrionomys glareolus) spontaneously develop stereotyped jumping in barren cages, already before the age of 1 month (= captivity-induced stereotypies or CIS). Large interindividual differences in the level of jumping exist. In this study, the effect of MK-801 on various behaviours of bank voles, and in particular the relationship between CIS and PHIS, was investigated by repeated administration of MK-801 to stereotyping (ST) and non-stereotyping (NST) voles. The animals received nine daily s.c. injections of, respectively, saline and 0.3 mg/kg MK-801, with a 48-h break between both treatments. Their behaviour was visually recorded every 4 days. The results showed that jumping was neither evoked in NST, nor intensified in ST. Instead, in both ST and NST, PHIS consisting of intensive sniffing and locomotor stereotypy characterised by running in unidirectional circles were elicited. Furthermore, ST showed behavioural sensitisation for locomotor stereotypy, while in NST intensive sniffing was progressively enhanced. These results suggest that CIS and PHIS induced by MK-801 in bank voles are regulated, at least in part, by different neuronal mechanisms and that ST and NST could be predisposed to develop more easily one given PHIS than the other.