Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of G(z).
BACKGROUND
G(z) is a member of the G(i) G protein family associated with dopamine D2-like receptors; however, its functions remain relatively unknown. The aim of the present study was to investigate prepulse inhibition (PPI) of acoustic startle, locomotor hyperactivity and dopamine D2 receptor binding in mice deficient in the alpha subunit of G(z).


METHODS
We used automated startle boxes to assess startle and PPI after treatment with saline, amphetamine, apomorphine or MK-801. We used photocell cages to quantitate locomotor activity after amphetamine treatment. Dopamine D2 receptor density was determined by autoradiography.


RESULTS
Startle responses and baseline PPI were not different between the Galpha(z) knockout mice and wild-type controls (average PPI 46+/-4 vs 49+/-3%, respectively). Amphetamine treatment caused a marked disruption of PPI in Galpha(z) knockouts (average PPI 22+/-2%), but less so in controls (average PPI 42+/-3%). Similar genotype-dependent responses were seen after apomorphine treatment (average PPI 23+/-3% vs 40+/-3%), but not after MK-801 treatment (average PPI 29+/-5 vs 33+/-2%). Amphetamine-induced locomotor hyperactivity was greater in Galpha(z) knockouts than in controls. There was no difference in the density of dopamine D2 receptors in nucleus accumbens.


CONCLUSIONS
Mice deficient in the alpha subunit of G(z) show enhanced sensitivity to the disruption of PPI and locomotor hyperactivity caused by dopaminergic stimulation. These results suggest a possible role for G(z) in neuropsychiatric illnesses with presumed dopaminergic hyperactivity, such as schizophrenia.
van den Buuse
M
M
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, 155 Oak Street, Parkville, Victoria 3052, Australia. mvandenbuuse@mhri.edu.au
Martin
S
S
Brosda
J
J
Leck
K J
KJ
Matthaei
K I
KI
Hendry
I
I
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001345:Autoradiography; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013216:Reflex, Startle
D044385:GTP-Binding Protein alpha Subunits; C490964:Gnaz protein, mouse; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016291:Dizocilpine Maleate; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine