LONG-LASTING CONSEQUENCES OF CHRONIC TREATMENT WITH THE DOPAMINE AGONIST QUINPIROLE FOR THE UNDRUGGED BEHAVIOR OF RATS

This study asks whether apart from behavioral sensitization, chronic treatment with the D2 dopamine agonist quinpirole produces long-term effects on undrugged behavior. Rats (n = 12) were pretreated with 10 injections of quinpirole (0.5 mg/kg every 4 days in activity cages), producing a 6-fold increase in locomotor activity. Ten days later, their undrugged behavior was assessed in a large open field, and their spatial learning in a Morris water maze; the entire procedure was repeated 3 months later. Control animals were pretreated with saline and tested in the open field either undrugged (n = 12) or with acute quinpirole (n = 12); only undrugged controls were used for spatial learning. Results indicate that quinpirole pretreatment results in persisting changes that can be characterized as a reduction in the rat's freedom of movement. Compared to vehicle controls, quinpirole pretreated rats turn with a more rigid body, show more repetitive travel along the same routes in the open field, and perseverate more during extinction in the water maze. These effects are weaker at 3 months postsensitization. In all other respects (level of activity in the open field and acquisition learning) Sensitized rats behave no differently from vehicle controls. Changes in undrugged behavior in the open field resemble the effects of quinpirole but are smaller in magnitude. It is suggested that the alteration in undrugged behavior reflects compensatory behavioral adaptation to the exaggerated hyperactivity induced by quinpirole.