Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of G sub(z)

• Published in: Psychopharmacology 2006-12, Vol.183 (3), p.358-367
• Main Authors: Buuse, M, Martin, S, Brosda, J, Leck, K J, Matthaei, KI, Hendry, I
• Format: Article
• Language: English
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-005-0181-6

Rationale: G sub(z) is a member of the G sub(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 sub(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 G alpha sub(z) knockout mice and wild-type controls (average PPI 46 plus or minus 4 vs 49 plus or minus 3%, respectively). Amphetamine treatment caused a marked disruption of PPI in G alpha sub(z) knockouts (average PPI 22 plus or minus 2%), but less so in controls (average PPI 42 plus or minus 3%). Similar genotype-dependent responses were seen after apomorphine treatment (average PPI 23 plus or minus 3% vs 40 plus or minus 3%), but not after MK-801 treatment (average PPI 29 plus or minus 5 vs 33 plus or minus 2%). Amphetamine-induced locomotor hyperactivity was greater in G alpha sub(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 sub(z) show enhanced sensitivity to the disruption of PPI and locomotor hyperactivity caused by dopaminergic stimulation. These results suggest a possible role for G sub(z) in neuropsychiatric illnesses with presumed dopaminergic hyperactivity, such as schizophrenia.