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-m ovement, circling, and a high level of ambulatory activity. Heterozygo us (stg/+) littermates display normal spontaneous behaviors. In this s tudy, stargazers and their unaffected littermates were compared in the ir behavioral responses to both stimulation and inhibition of dopamine D-2/D-3 receptors, using quinpirole and haloperidol. Stargazers were observed to yawn a significantly fewer number of times than littermate s 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 moveme nt in the mutants that was both time- and dose-dependent. In normal li ttermates, HAL inhibited locomotor activity and produced catalepsy in a time- and dose-dependent manner. In stargazers, both doses of HAL in hibited 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 th e present evidence of D-2/D-3 receptor subsensitivity suggest that sta rgazers possess a genetically mediated dysfunction of the central dopa minergic system.