Peptide ACTH4-7-PGP: Effects on Various Types of Pain and Pain-Induced Behavior in Rats after Systemic and Central Administration.

The effects of peptide ACTH4-7-PGP (Semax) were studied in 12 min after its intraperitoneal (in doses of 5, 15, 50, 150, and 450 µg/kg) or intracerebroventricular (in doses of 16, 40, and 400 pg) administration to rats with different types of pain and pain-induced behavior. It was found that the peptide increased pain sensitivity and induced avoidance behavior during thermal stimulation ("hot plate" test), but had an analgesic effect (more pronounced after central administration) and weakened emotional-affective behavior in electrocutaneous stimulation of the paws (foot-shock model) and tail in rats. It was shown that changes in activity of supraspinal brain structures were of primary importance in the mechanism of action on the nociceptive process and the formation of behavior.

Effects of Tripeptide Gly-His-Lys in Pain-Induced Aggressive-Defensive Behavior in Rats.

We studied the effect of Gly-His -Lys tripeptide administered intraperitoneally in doses of 5, 15, 50 and 150 µg/kg on pain-induced aggressive-defensive behavior. A foot-shock model of aggression in rats grouped in pairs in an electrified chamber was used. Analgesic and antiaggresiogenic effects of the peptide were demonstrated. It was found the L-lysine residue plays the key role in these effects, because they were observed under the influence of L-lysine administration in doses close to its equimolar content in the studied tripeptide.

Anxiolytic effects of Gly-His-Lys peptide and its analogs.

Intraperitoneal administration of tripeptide Gly-His-Lys to male rats in doses of 0.5, 5, and 50 µg/kg 12 min before the start of the experiment produced an anxiolytic effect in the elevated plus maze test manifested in an increase in the time spent in open arms and shortened time spent in the closed arms. The anxiolytic effect was most pronounced after injection of 0.5 µg/kg peptide and decreased with increasing the dose of the peptide. Replacement of L-lysine with D-lysine in the tripeptide molecule was accompanied by a significant weakening of the neurotropic effects in all studied doses. Attachment of D-alanine to N- or C-terminus of Gly-His-Lys peptide leveled its anxiolytic action in all doses; significant changes in some measures of increased anxiety after administration at 50 µg/kg were found.

[Effect of Gly-His-Lys peptide and its analogs on pain sensitivity in mice].

The intraperitoneal administration of Gly-His-Lys tripeptide to male BALB/c mice 12 min before the beginning of the study at doses 0.5, 1.5, 5, 15, and 50 mg/kg produced analgesic effect in the hot-plate test, which was manifested by an increase in the duration of the latent period of the paw-licking reaction. The replacement of L-lysine by D-lysine in the tripeptide molecule was accompanied by significant weakening of the analgesic effect after administration in the same doses. The attachment of D-alanine to N- or C-end of Gly-His-Lys peptide led to leveling of the analgesic effect. On the contrary, after the administration of these analogs, the duration of the latent period of the paw-licking reaction was increased in almost all experimental groups of animals and reached in some cases significant differences that were indicative of the manifestation of algic effects of the modified peptides.

Neurotropic effects of L-lysine in formation of pain-induced behavior.

In experiments on Wistar rats L-lysine (0.15, 0.5, 1.5, 5.0, 15.0, and 50.0 microg/kg intraperitoneally) exhibited a dose-dependent algic effect during electrocutaneous stimulation of the tail and dose-dependent effects in aggressive defense behavior caused by electrical painful stimulation of paws. It was found that the effect of L-lysine depended on situation determining the predominance of defense or aggression, rather than on the intensity of painful stimulation.

Effects of L-arginine on various types of pain sensitivity.

Intraperitoneal injection of L-arginine to male Wistar rats 12 min before the start of the experiment produced a nociceptive effect on models of electrocutaneous stimulation of the tail or hot-plate test and increased nociceptive behavior due to high sensitivity of supraspinal nociceptive structures to this compound. The nociceptive effect of this amino acid was more pronounced and persistent under conditions of electrocutaneous stimulation.