Effect of long-term haloperidol treatment on striatal neuropeptides: Relation to stereotyped behavior

Behavioral and biochemical responses to D-1 and D-2 dopamine (DA) agonists were used to evaluate the participation of striatal peptidergic mechanisms in the motor function alterations that attend chronic neuroleptic :treatment. Rats, given haloperidol (1 mg/kg, s.c.) for 21 consecutive days, were randomly allocated to one of the following treatments: the D-1 agonist SKF 38393, the D-2 agonist quinpirole, their combination or saline. Stereotyped behavior and neuropeptide levels were evaluated after 5 days treatment and 4 days washout. Haloperidol increased most oral behaviors including licking, chewing and biting as well as striatal enkephalin and somatostatin levels. Subsequent treatment with SKF 38393 diminished the haloperidol-induced increase in licking and chewing; quinpirole reduced chewing behavior. The administration of both agonists together decreased chewing and biting. Neither DA agonist alone, nor their combination, reduced the haloperidol-induced increase in enkephalin levels. Both SKF 38393 and quinpirole, when given alone, tended to decrease the haloperidol-induced increase in somatostatin levels; when both the D, and D, agonists were administered together, somatostatin levels declined significantly. These results suggest that somatostatin- but not enkephalin-containing striatal neurons contribute to the expression of haloperidol-induced stereotypies.