Evidence for genetically mediated dysfunction of the central dopaminergic system in the stargazer rat

The stargazer rat is an autosomal recessive mutant (homozygous stg/stg) that displays abnormal behavior, characterized by stereotypic head-movement, circling, and a high level of ambulatory activity. Heterozygous (stg/+) littermates display normal spontaneous behaviors. In this study, stargazers and their unaffected littermates were compared in their behavioral responses to both stimulation and inhibition of dopamine D2/D3 receptors, using quinpirole and haloperidol. Stargazers were observed to yawn a significantly fewer number of times than littermates in response to (--)-quinpirole (50 mu g/kg, IP). Haloperidol (HAL 0.1 mg/kg and 0.3 mg/kg, SC) caused a decrease in stereotypic head-movement in the mutants that was both time- and dose-dependent. In normal littermates, HAL inhibited locomotor activity and produced catalepsy in a time- and dose-dependent manner. In stargazers, both doses of HAL inhibited locomotor activity to a similar degree as in the littermates. However, no catalepsy was detectable in the mutants using 0.1 mg/kg of HAL. A dose of 0.3 mg/kg HAL was only weakly cataleptogenic. Overall, the spectrum of abnormal behaviors expressed by the stargazers and the present evidence of D2/D3 receptor subsensitivity suggest that stargazers possess a genetically mediated dysfunction of the central dopaminergic system.