[Abstract Title]. - Society for Neuroscience

including muscarinic, serotonergic and glutamatergic signaling systems. It is of interest,
therefore, that phospholipase C-β1 (PLC-β1) acts as a point of convergence for these pathways
during cortical development and plasticity. These signaling pathways, furthermore, are
susceptible to modulation by RGS4, one of the more promising candidate genes for
schizophrenia. PLC-β1 knockout mice were behaviorally assessed on tests including fear
conditioning, elevated plus maze, and the Y maze. In situ hybridization was used to assess RGS4
expression. We found that PLC-β1 knockout mice display abnormal anxiety profiles on some,
but not all measures assessed, including decreased anxiety on the elevated plus maze. We also
show memory impairment and a complete absence of acquisition of hippocampal-dependent fear
conditioning. Furthermore, at a molecular level, we demonstrate dramatic changes in expression
of RGS4 mRNA in selective regions of the PLC-β1 knockout mouse brain, particularly the CA1
region of the hippocampus. These results validate the utility of the PLC-β1 knockout mouse as a
model of schizophrenia, including molecular and cellular evidence for disrupted cortical
maturation and associated behavioral endophenotypes.
Disclosures: C.E. McOmish , None; E. Burrows, None; M. Howard, None; A.J. Hannan,
None.
Poster
255. Mood Disorders: Animal Models and Treatment Effects II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 255.1/Y16
Topic: C.15.h. Affective disorders: Animal models
Support: CIHR
Title: Corticolimbic cannabinoid CB1 receptor activity regulates stress coping behavior in the
forced swim test
Authors: *R. J. MCLAUGHLIN 1 , M. N. HILL 2 , A. C. MORRISH 2 , B. B. GORZALKA 2 ;
1 Dept Psych, 2 Psychology, Univ. of British Columbia, Vancouver, BC, Canada
Abstract: In recent years, the endocannabinoid system has emerged as an important new target
in the development of novel antidepressant drugs. However, a discrepancy exists in the literature
such that antidepressant effects have been demonstrated following systemic administration of
both CB1 receptor agonists and antagonists. These differential effects are likely mediated by
CB1 receptor activation/antagonism within distinct neural circuits. Administration of a CB1
receptor agonist into the dorsal hippocampus or ventromedial prefrontal cortex (vmPFC) has
been found to elicit antidepressant-like effects in the forced swim test; however, no study to date