Gly-His-Lys (GHK) peptide demonstrates dose-dependent anxiolytic effects in male rats

Anxiety disorders represent a significant global health burden, often managed with pharmacotherapies like benzodiazepines or selective serotonin reuptake inhibitors (SSRIs). While effective, these treatments can carry risks of dependence, side effects, or delayed onset of action, highlighting a critical need for novel anxiolytic agents. Peptides, with their high specificity and generally favorable safety profiles, offer a promising avenue. Gly-His-Lys (GHK) is a naturally occurring human tripeptide known for its regenerative and anti-inflammatory properties, but its potential neurotropic and anxiolytic actions have been less explored, presenting a gap this research aims to address.

Researchers investigated the anxiolytic potential of the tripeptide Gly-His-Lys (GHK) and its analogs in male rats. The study involved intraperitoneal (IP) administration of GHK at three distinct doses: 0.5 μg/kg, 5 μg/kg, and 50 μg/kg. Peptides were administered 12 min before the start of the experiment. The primary endpoint was anxiolytic behavior, assessed using the elevated plus maze test. Control groups were not explicitly detailed in the abstract but are implied by the comparative analysis of GHK doses and its analogs. Analogs tested included GHK with L-lysine replaced by D-lysine, and GHK with D-alanine attached to either the N- or C-terminus.

Intraperitoneal administration of Gly-His-Lys (GHK) to male rats produced a clear anxiolytic effect in the elevated plus maze test. This was evidenced by a significant increase in the time spent in the open arms and a shortened time spent in the closed arms, both classic indicators of reduced anxiety. The anxiolytic effect was notably dose-dependent, with the most pronounced effect observed at the lowest dose of 0.5 μg/kg GHK. Higher doses of 5 μg/kg and 50 μg/kg showed a diminished anxiolytic response, suggesting an optimal therapeutic window at lower concentrations. Alterations to the GHK molecule significantly impacted its neurotropic activity. > Replacement of L-lysine with D-lysine in the tripeptide molecule led to a significant weakening of the neurotropic effects across all tested doses. Furthermore, the attachment of D-alanine to either the N- or C-terminus of the GHK peptide completely leveled its anxiolytic action at all doses, although some minor changes in anxiety measures were noted after administration at 50 μg/kg.