Acoustic startle response and sensorimotor gating in a genetic mouse model for the Y1 receptor.
Recent research has highlighted a potential role for neuropeptide Y (NPY) and its Y(1) receptor in the development of schizophrenia. Genetic as well as molecular biological studies have demonstrated reduced levels of NPY in schizophrenia patients. Importantly, Y(1) receptors may mediate some of the potential effects of NPY on schizophrenia, as decreased Y(1) receptor expression has been found in the lymphocytes of schizophrenia patients. To clarify NPY's role in schizophrenia, we investigated a genetic animal model for Y(1) deficiency in regard to (i) acoustic startle response (ASR), (ii) habituation to ASR and (iii) sensorimotor gating [i.e. prepulse inhibition (PPI)] using two different PPI protocols. Mutant and wild type-like mice were screened for baseline behaviours and after pharmacological challenge with the psychotropic drugs dexamphetamine (DEX) and MK-801. Y(1) knockout mice (Y(1)(-/-)) showed a moderate reduction of the ASR and an impaired ASR habituation at baseline and after DEX treatment. The baseline PPI performance of Y(1) mutant mice was unaltered their response to DEX and MK-801 challenge was moderately different compared to control mice, which was dependent on the PPI protocol used. MK-801 challenge had a protocol-dependent differential effect in Y(1)(-/-) mice and DEX a more pronounced impact at the highest prepulse intensities. In conclusion, it appears that the Y(1) receptor influences the acoustic startle response and its habituation but does not play a major role in sensorimotor gating. Further explorations into the effects of Y(1) deficiency seem valid.
Karl
T
T
Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. t.karl@schizophreniaresearch.org.au
Chesworth
R
R
Duffy
L
L
Herzog
H
H
D000818:Animals; D003913:Dextroamphetamine / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D013216:Reflex, Startle / Q000187:drug effects* / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D055139:Sensory Gating / Q000187:drug effects* / Q000235:genetics
D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D016291:Dizocilpine Maleate; D003913:Dextroamphetamine