Intranigral stimulation of oral movements by [Pro9] substance P, a neurokinin-1 receptor agonist, is enhanced in chronically neuroleptic-treated rats.
Bilateral intranigral infusions of three different peptide agonists were made in rats exposed to fluphenazine decanoate, 30 mg/kg/month (FLU) or vehicle (CON) for seven months. Oral movements were monitored repeatedly 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, caused a significant increase of VCM in both pretreatment groups, lasting 7 min after the infusion. The VCM response to [Pro9]Substance P in the FLU group was significantly higher than in the CON group. A NK2 agonist [Lys5, MeLeu9, Nle10]Neurokinin A(4-10) (2.5 nmol) failed to produce significant changes in oral activity. A Leu-enkephalin analogue [D-Ala2,D-Leu5]enkephalin (3.8 nmol) induced a massive biting behavior in both FLU and CON rats. Using VCM as a behavioral assay, an increased nigral sensitivity to a NK1 agonist is demonstrated in rats chronically exposed to neuroleptics. No corresponding alterations could be ascribed for the NK2 receptor agonist or the Leu-enkephalin analogue.
Liminga
U
U
Department of Psychiatry at Ulleråker, Uppsala University, Sweden.
Gunne
L M
LM
D000818:Animals; D005260:Female; D005476:Fluphenazine / Q000031:analogs & derivatives* / Q000633:toxicity; D008409:Mastication / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D018040:Receptors, Neurokinin-1; C067285:substance P, Pro(9)-; D013373:Substance P; C011825:fluphenazine depot; D005476:Fluphenazine