title: Tyr-MIF-1 attenuates development of tolerance to spiperone-induced catalepsy in rats.
abstract: Because the tripeptide MIF-1 (Pro-Leu-Gly-NH2) is known to attenuate the effects of neuroleptic-induced catalepsy as well as neuroleptic-induced proliferation of dopamine (DA) receptors, we studied the related naturally occurring peptide, Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) for similar properties. Male rats were treated SC for 11 consecutive days with either the DA D1 receptor antagonist SCH 23390 HCl (0.50 mg/kg per day), the DA D2 receptor antagonist spiperone HCl (0.30 mg/kg per day), or vehicle. Half the rats were cotreated daily with Tyr-MIF-1 (1.0 mg/kg per day). The cataleptic effects of SCH 23390 were not altered by Tyr-MIF-1. Tolerance to SCH 23390-induced catalepsy did not develop during the 11-day treatment, and Tyr-MIF-1 had no effect on SCH 23390-induced catalepsy. However, tolerance developed to spiperone-induced catalepsy, and Tyr-MIF-1 attenuated this development of tolerance (p < 0.001). Locomotor and stereotyped activities of the DA D1 and D2 agonists, SKF 39393 (3.0 mg/kg) and quinpirole (3.0 mg/kg) were not affected by Tyr-MIF-1 after treatment with the DA antagonists was discontinued. Tyr-MIF-1 did not alter the Bmax or Kd for in vitro binding of [3H]SCH 23390 and [3H]spiperone to homogenates of the striatum. These findings indicate that Tyr-MIF-1 is able to selectively affect the development of receptor tolerance to a DA D2 receptor antagonist, and that this effect is unrelated to changes in affinity or numbers of D2 receptors.
authors.affiliation: Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City 37614.
authors.forename: R M
authors.initials: RM
authors.lastname: Kostrzewa
authors.forename: A J
authors.initials: AJ
authors.lastname: Kastin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced*; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone