Szczegóły publikacji
Opis bibliograficzny
Naltrexone dose-selectively modulates goal-directed behavior and the hypothalamic proteome in rats / Natalia Malikowska-Racia, Przemysław Mielczarek, Piotr Popik // Pharmacological Reports ; ISSN 1734-1140 . — 2025 — vol. 77 iss. 4, s. 983–998. — Bibliogr. s. 996-998, Abstr. — Publikacja dostępna online od: 2025-05-28. — P. Mielczarek - afiliacja: Laboratory of Proteomics and Mass Spectrometry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
Autorzy (3)
- Malikowska-Racia Natalia
- Mielczarek Przemysław
- Popik Piotr
Słowa kluczowe
Dane bibliometryczne
| ID BaDAP | 166262 |
|---|---|
| Data dodania do BaDAP | 2026-03-13 |
| Tekst źródłowy | URL |
| DOI | 10.1007/s43440-025-00735-4 |
| Rok publikacji | 2025 |
| Typ publikacji | artykuł w czasopiśmie |
| Otwarty dostęp |  |
| Creative Commons | |
| Czasopismo/seria | Pharmacological Reports |
Abstract
Background Naltrexone is an opioid receptor antagonist that can modulate reward processing in opposite directions depending on the dose. Whether naltrexone similarly affects motivation remains unexplored. This study investigates the effects of naltrexone on behavioral measures of motivation and search for potential mechanisms, including the endogenous opioid pathway dependent on proopiomelanocortin (POMC). Methods Male Sprague Dawley rats received naltrexone (0.01, 0.1, or 1 mg/kg, ip) for two weeks. During this period, rats were tested daily using a progressive ratio schedule of reinforcement (PR) test and effort-based choice (EBC) that address motivational vigor, directedness, and effort-based decision-making. After tests, the hypothalami were collected for proteomic analysis using data-independent acquisition (DIA). Results Low-dose naltrexone (0.01 mg/kg; LDN) transiently increased PR response vigor without altering decision-making in EBC. At 0.1 mg/kg, but not at the high dose of 1 mg/kg, it impaired effort-based decision-making and goal-directedness. Proteomic analysis correlated LDN with the downregulation of a growth hormone (GH) pathway and altered G protein-coupled receptors (GPCR) signaling. Naltrexone’s intermediate dose predominantly impacted proteins involved in neural growth, while the 1 mg/kg dose affected proteins related to gene regulation. Conclusions Different doses of naltrexone had varying effects on motivational measures and the rat’s hypothalamic proteome. Naltrexone 0.1 mg/kg impaired motivational directedness and effort-based decision-making that corresponds to reduced reward signaling due to opioid blockade. In contrast, LDN enhanced vigor, but only early in the treatment. Naltrexone had no effects on the POMC-dependent endogenous opioid pathway, suggesting that a different mechanism underlies its motivational effects.
