INTRANIGRAL STIMULATION OF ORAL MOVEMENTS BY [PRO(9)] SUBSTANCE-P, A NEUROKININ-1 RECEPTOR AGONIST, IS ENHANCED IN CHRONICALLY NEUROLEPTIC-TREATED RATS

Bilateral intranigral infusions of three different peptide agonists we re made in rats exposed to fluphenazine decanoate, 30 mg/kg/month (FLU ) or vehicle (CON) for seven months. Oral movements were monitored rep eatedly during the neuroleptic pretreatment period, as well as before the intranigral infusion and during a 90-min period postinfusion. The FLU group had an increased frequency of vacuous chewing movements (VCM )during the pretreatment period in comparison to controls. Intranigral infusion of the neurokinin-1 (NK1) receptor agonist, [Pro9]Substance P (2.5 nmol on each side), 5-7 weeks after the last FLU injection, cau sed a significant increase of VCM in both pretreatment groups, lasting 7 min after the infusion. The VCM response to [Pro9]Substance P in th e FLU group was significantly higher than in the CON group. A NK2 agon ist [LyS5, MeLeu9, Nle10]Neurokinin A(4-10) (2.5 nmol) failed to produ ce significant changes in oral activity. A Leu-enkephalin analogue [D- Ala2, D-Leu5]enkephalin (3.8 nmol) induced a massive biting behavior i n both FLU and CON rats. Using VCM as a behavioral assay, an increased nigral sensitivity to a NK1 agonist is demonstrated in rats chronical ly exposed to neuroleptics. No corresponding alterations could be ascr ibed for the NK2 receptor agonist or the Leu-enkephalin analogue.