Sensitization of rotation behavior in rats with unilateral 6-hydroxydopamine or kainic acid-induced striatal lesions.

Following unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra or unilateral kainic acid (KA) lesions of the striatum rats displayed rotation behavior in response to apomorphine (0.25 mg/kg SC or 1 mg/kg SC for the 6-OHDA- and KA-lesioned rats respectively). Three to five days following the initial apomorphine challenge rats were challenged under identical conditions with the same dose of apomorphine received previously. Both 6-OHDA- and KA-lesioned rats demonstrated a significant increase in the total number of rotations. Following a subsequent challenge with apomorphine, rats showed further increases in the total number of rotations. With the second and the subsequent apomorphine challenges there were significant increases in the maximal number of rotations, a significant decrease in the time of onset of rotation behavior and in some cases an increase in the duration of the rotation behavior. These increases in rotation behavior following repeated challenges with apomorphine indicate a supersensitivity to dopamine receptor agonists distinct from that elicited by lesions and chronic antagonist treatments. Furthermore, the utility of the rotation behavior model for testing the efficacy of dopaminergic agonists might be compromised if repeated challenges in individual animals are employed.

Chronic treatment with MK-801 increases the quinolinic acid-induced loss of D-1 dopamine receptors in rat striatum.

Following withdrawal from short-term treatment with the non-competitive N-methyl-d-aspartate receptor antagonist MK-801 (1 mg/kg per day) there was no significant change in the Bmax or KD of [3H]SCH23390 binding to dopamine D-1 receptors in rat striatum. Intrastriatal injection of the excitotoxin quinolinic acid (100 nmol) produced a significant decrease in [3H]SCH23390 binding. In rats withdrawn from chronic MK-801 treatment quinolinic acid produced a significantly greater loss of [3H]SCH23390 binding sites than in rats not treated with MK-801. These data indicated that striatal neurons are hypersensitive to the neurotoxic actions of quinolinic acid following withdrawal from chronic MK-801 treatment.