Natalia Malikowska-Racia, Przemysław Mielczarek, Piotr Popik
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引用次数: 0
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.
期刊介绍:
Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures.
Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology.
Studies of plant extracts are not suitable for Pharmacological Reports.