Peptide-induced grooming behavior and caudate nucleus dopamine release.
Florijn. W J WJ; Holtmaat. A J AJ; de Lang. H H; Spierenburg. H H; Gispen. W H WH; Versteeg. D H DH
Key Findings
- Intracerebroventricular ACTH-(1-24) and the alpha‑MSH agonist [Nle4,D-Phe7]alpha‑MSH both increase grooming behavior in rats.
- Both peptides raise extracellular dopamine in the caudate nucleus to about 150% of baseline, without changing its metabolite DOPAC.
- A shorter ACTH fragment (ACTH‑(7‑16)-NH2) does not trigger grooming or dopamine release, indicating the effect depends on specific peptide sequences.
Practical Outcomes
- For biohackers, this study suggests that MSH‑like peptides can influence brain dopamine pathways, which might affect mood or reward, but the experiments used direct brain injection—not the typical skin or subcutaneous routes used by humans. The findings are too early and mechanistic to change dosing protocols for melanotan‑I, but they hint that chronic use could have central nervous system effects worth monitoring.
Summary
In rats, giving a brain‑injected form of ACTH or a synthetic alpha‑MSH drug caused the animals to groom a lot and raised dopamine levels in a brain area called the caudate nucleus. The effect was linked to the peptide’s ability to activate the alpha‑melanocyte stimulating hormone receptor, but the same effect wasn’t seen with a shorter ACTH fragment. Tolerance built up to the grooming behavior after one dose, but not to the dopamine rise.
Abstract
We simultaneously measured the display of grooming behavior and, by monitoring the extracellular dopamine concentration via transversal microdialysis, the release of dopamine in the caudate nucleus in freely moving rats after i.c.v. administration of 1 micrograms adrenocorticotropic hormone-(1-24) (ACTH-(1-24)). During a period of 1 h after administration of the peptide, the incidence of excessive grooming behavior was increased. Concomitantly, the concentration of dopamine in the caudate nucleus dialysates was significantly increased (maximal effect 151% of basal release) whereas that of its metabolite DOPAC was unchanged. The potent alpha-melanocyte stimulating hormone (alpha-MSH) receptor agonist, [Nle4,D-Phe7]alpha-MSH, induced grooming behavior and stimulated caudate nucleus dopamine release (maximal effect 148% of basal release) whereas ACTH-(7-16)-NH2 did neither induce grooming behavior nor cause an increase in caudate nucleus dopamine release. Single-dose tolerance was observed for ACTH-induced grooming but not for ACTH-induced dopamine release. These data are in support of the proposed involvement of brain dopamine systems in grooming behavior of the rat but at the same time suggest that the effect of ACTH/MSH-like peptides on dopaminergic transmission in the caudate nucleus is proximal to the final neural pathway involved in ACTH-induced grooming behavior.
Study Information
pubmed
1993
1993-10-15T00:00:00.000Z
10.1016/0006-8993(93)90151-c