Rebecca J Ralph1, S Barak Caine. 1. Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
Abstract
RATIONALE: Prepulse inhibition (PPI) and locomotor activity have been used to investigate the effects of antipsychotic and stimulant drugs and their underlying dopaminergic mechanisms. Whereas D2-like agonists consistently decreased PPI and increased locomotion in rats in previous studies, we recently reported that these hallmark behavioral effects were not observed in several mouse strains. Nevertheless, we recently identified three mouse strains (C3H/HeJ, SPRET/EiJ, and CAST/EiJ) that exhibited locomotor hyperactivity after administration of a selective D2-like agonist. OBJECTIVES: We hypothesized that, similar to rats, C3H/HeJ, SPRET/EiJ, and CAST/EiJ mice would exhibit decreased PPI after administration of a D2-like agonist. RESULTS: Administration of the D2-like agonist quinelorane dose-dependently decreased PPI in C3H/HeJ and SPRET/EiJ mice. In agreement with previous reports in rats and other strains of mice, the D1-like agonist R-6-Br-APB also decreased PPI in C3H/HeJ and SPRET/EiJ mice. In contrast, CAST/EiJ mice had low levels of baseline PPI in our standard test session and quinelorane and R-6-Br-APB had no effect on PPI under those conditions. Through the optimization of session parameters, we obtained higher baseline PPI in CAST/EiJ mice and found that quinelorane but not R-6-Br-APB decreased PPI. In summary, similar to rats and unlike previous published reports on several strains of mice, we have now identified three strains of mice in which a D2-like agonist decreased PPI. CONCLUSIONS: The C3H/HeJ, SPRET/EiJ, and CAST/EiJ mice may more closely mirror the Sprague Dawley rat than most other mouse strains and may confer advantages in cross-species behavioral pharmacology studies related to D2 receptor function.
RATIONALE: Prepulse inhibition (PPI) and locomotor activity have been used to investigate the effects of antipsychotic and stimulant drugs and their underlying dopaminergic mechanisms. Whereas D2-like agonists consistently decreased PPI and increased locomotion in rats in previous studies, we recently reported that these hallmark behavioral effects were not observed in several mouse strains. Nevertheless, we recently identified three mouse strains (C3H/HeJ, SPRET/EiJ, and CAST/EiJ) that exhibited locomotor hyperactivity after administration of a selective D2-like agonist. OBJECTIVES: We hypothesized that, similar to rats, C3H/HeJ, SPRET/EiJ, and CAST/EiJ mice would exhibit decreased PPI after administration of a D2-like agonist. RESULTS: Administration of the D2-like agonist quinelorane dose-dependently decreased PPI in C3H/HeJ and SPRET/EiJ mice. In agreement with previous reports in rats and other strains of mice, the D1-like agonist R-6-Br-APB also decreased PPI in C3H/HeJ and SPRET/EiJ mice. In contrast, CAST/EiJ mice had low levels of baseline PPI in our standard test session and quinelorane and R-6-Br-APB had no effect on PPI under those conditions. Through the optimization of session parameters, we obtained higher baseline PPI in CAST/EiJ mice and found that quinelorane but not R-6-Br-APB decreased PPI. In summary, similar to rats and unlike previous published reports on several strains of mice, we have now identified three strains of mice in which a D2-like agonist decreased PPI. CONCLUSIONS: The C3H/HeJ, SPRET/EiJ, and CAST/EiJ mice may more closely mirror the Sprague Dawley rat than most other mouse strains and may confer advantages in cross-species behavioral pharmacology studies related to D2 receptor function.
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