Isolation rearing in rats: effect on expression of synaptic, myelin and GABA-related immunoreactivity and its utility for drug screening via the subchronic parenteral route.
Depriving weaned rats of social contact by rearing them in isolation brings about a spectrum of behavioural and neuropathological changes in adulthood which resemble some of the characteristics observed in schizophrenia. Hence, isolation rearing provides a non-pharmacological means to induce in an animal model certain aspects of schizophrenia with a neurodevelopmental origin. We compared the prepulse inhibition and locomotor activity behaviours in group-reared and isolation-reared rats in the context of determining the robustness of any behavioural changes following a subchronic parenteral drug administration protocol. The expression of synaptic, myelin and GABA-related proteins was also assessed in the brains of these rats using semi-quantitative fluorescence immunohistochemistry. Compared to their group-reared counterparts, isolation-reared rats displayed disruption in prepulse inhibition which was lost after repeated testing and subchronic vehicle administration. However, isolation-reared rats showed open-field hyperlocomotion post-subchronic vehicle treatment compared to group-reared rats. Isolation rearing resulted in reduced expression of synaptophysin, synapsin I, myelin basic protein and GABA(B1) receptor proteins, along with an increase in 2',3'-cyclic nucleotide 3'-phosphodiesterase. Of the brain areas examined these observed changes were localised to the hippocampal regions and the substantia nigra. These results suggest an alteration in the synaptic, myelin and GABA-related functions in the brains of isolation-reared rats that displayed behavioural anomalies. Since dysfunction in these systems has also been implicated in schizophrenia, our findings provide additional evidence to support the use of isolation rearing for schizophrenia research; however, its use in the screening of putative antipsychotics following subchronic administration needs to be undertaken warily.
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia. ann.lim@monash.edu
Ann Li
AL
Lim
David Alan
DA
Taylor
Daniel Thomas
DT
Malone
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009186:Myelin Sheath / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism; D013216:Reflex, Startle / Q000502:physiology; D055139:Sensory Gating / Q000502:physiology; D012934:Social Isolation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid