Neuroscience 2002 Abstract
| Presentation Number: | 263.4 |
|---|---|
| Abstract Title: | Behavioral Characterization of PDE-1B Knockout Mice. |
| Authors: |
McCarthy, S. A.*1
; Fujiwara , R. A.1
; Repaske, D.2
; Siuciak, J. A.1
1CNS, Pfizer, Groton, CT 2Children's Hospital Medical Center, University of Cincinnati, OH |
| Primary Theme and Topics |
Motor Systems - Basal Ganglia -- Transmitters and receptors |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Intracellular Signalling Pathways<br />-- Second messengers |
| Session: |
263. Basal ganglia: transmitters and receptors--expression II Poster |
| Presentation Time: | Monday, November 4, 2002 11:00 AM-12:00 PM |
| Location: | Hall A2-B3 F-40 |
| Keywords: | dopamine, haloperidol, locomotor, striatum |
PDE1B is a calcium dependent cyclic nucleotide phosphodiesterase that is highly expressed in the striatum. Male and female wildtype (WT) and homozygous knockout mice (KO) mice were tested in a functional observational battery, as well as in a variety of behavioral assays including spontaneous locomotor activity, measures of pain sensitivity (hot plate and tail flick), anxiety (elevated plus maze), learning and memory (passive avoidance) and depression (forced swim test). No differences in were observed between WT and KO mice in any of these assays except for locomotor activity.
As previously reported (Chapin et al., SFN 2001), female KO mice showed significantly higher levels of baseline spontaneous locomotor activity compared to the female WT mice. KO mice also showed an exaggerated locomotor response to an acute methamphetamine (1 mg/kg) challenge. However, in additional studies, no differences in stimulant-induced locomotor activity were found between male or female WT and KO mice after PCP administration (3.2 mg/kg).
We have previously reported altered dopamine and serotonin turnover in the striatum of PDE1B knockout mice (Chapin et al., 2001). Therefore, the responsiveness of PDE1B KO mice to haloperidol, a D2 antagonist, was also determined. Preliminary studies using a single dose of haloperidol (3.2 mg/kg) showed significantly less catalepsy in female KO mice compared to WT female mice. There was a smaller non-significant difference between male KO and WT mice after haloperidol. These studies support a role for PDE1B in modulating dopaminergic activity in the CNS.
As previously reported (Chapin et al., SFN 2001), female KO mice showed significantly higher levels of baseline spontaneous locomotor activity compared to the female WT mice. KO mice also showed an exaggerated locomotor response to an acute methamphetamine (1 mg/kg) challenge. However, in additional studies, no differences in stimulant-induced locomotor activity were found between male or female WT and KO mice after PCP administration (3.2 mg/kg).
We have previously reported altered dopamine and serotonin turnover in the striatum of PDE1B knockout mice (Chapin et al., 2001). Therefore, the responsiveness of PDE1B KO mice to haloperidol, a D2 antagonist, was also determined. Preliminary studies using a single dose of haloperidol (3.2 mg/kg) showed significantly less catalepsy in female KO mice compared to WT female mice. There was a smaller non-significant difference between male KO and WT mice after haloperidol. These studies support a role for PDE1B in modulating dopaminergic activity in the CNS.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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