Repeated stimulation of D-1 dopamine receptors increases the circling response to bromocriptine in rats with a 6-OHDA lesion.

We have studied the effect of repeated injections of a specific D-1 agonist, (SKF 38393), on circling behaviour in response to a specific D-2 agonist (bromocriptine) and on striatal D-2 DA receptors in rats with a unilateral lesion of the nigrostriatal pathway. Two groups of rats were formed on the basis of their circling response to a first injection of SKF 38393: clear contralateral circling (SKF-positive) and no (or ipsiversive) circling (SKF-negative). A few days later, these rats were tested once for bromocriptine-induced circling. A repeated treatment of 8 injections of SKF 38393 over 4 days was started the next day. The animals were tested again for bromocriptine-induced circling at the end of the repeated treatment with the D-1 agonist. A third group of rats received only the 2 test injections of bromocriptine and a fourth group included intact control animals. During the repeated treatment, the D-1 agonist induced an increase of the circling response up to the fourth injection and a decrease thereafter in the SKF-positive group. This was followed by a pronounced increase of circling in response to the second injection of bromocriptine. This increased sensitivity appears to be due to the chronic treatment with SKF 38393 since animals that did not respond initially to the D-1 agonist (SKF-negative group) and those that received only 2 injections of bromocriptine showed no increase of their circling response. The treatments did not increase the affinity of [3H]spiperone binding for the striatal D-2 dopamine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)