Academic Journal
Maternal isocaloric fructose exposure selectively attenuates effort-based cocaine motivation and remodels mesostriatal dopaminergic and melanocortin receptor profiles in male rat offspring.
| Τίτλος: | Maternal isocaloric fructose exposure selectively attenuates effort-based cocaine motivation and remodels mesostriatal dopaminergic and melanocortin receptor profiles in male rat offspring. |
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| Συγγραφείς: | Witek K; Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, Kraków PL-31-343, Poland. Electronic address: witek@if-pan.krakow.pl., Wydra K; Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, Kraków PL-31-343, Poland. Electronic address: wydra@if-pan.krakow.pl., Suder A; Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, Kraków PL-31-343, Poland. Electronic address: suder@if-pan.krakow.pl., Filip M; Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, Kraków PL-31-343, Poland. Electronic address: mal.fil@if-pan.krakow.pl. |
| Πηγή: | Behavioural brain research [Behav Brain Res] 2026 Jun 25; Vol. 508, pp. 116222. Date of Electronic Publication: 2026 Apr 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8004872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7549 (Electronic) Linking ISSN: 01664328 NLM ISO Abbreviation: Behav Brain Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| Ιατρικοί όροι (MeSH): | Motivation*/drug effects , Motivation*/physiology , Cocaine*/administration & dosage , Cocaine*/pharmacology , Prenatal Exposure Delayed Effects*/metabolism , Fructose*/pharmacology , Fructose*/administration & dosage , Receptor, Melanocortin, Type 4*/metabolism , Receptor, Melanocortin, Type 4*/drug effects , Drug-Seeking Behavior*/drug effects , Drug-Seeking Behavior*/physiology , Dopamine Uptake Inhibitors*/administration & dosage , Dopamine Uptake Inhibitors*/pharmacology, Receptors, Dopamine D2/metabolism ; Receptors, Dopamine D2/drug effects ; Nucleus Accumbens/metabolism ; Nucleus Accumbens/drug effects ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D1/drug effects ; Cocaine-Related Disorders/metabolism ; Corpus Striatum/metabolism ; Corpus Striatum/drug effects ; Extinction, Psychological/drug effects ; Behavior, Animal/drug effects ; Animals ; Male ; Female ; Pregnancy ; Rats ; Rats, Wistar ; Self Administration ; Mesolimbic System |
| Περίληψη: | Objective: Preclinical evidence suggests that maternal fructose (FRU) exposure during pregnancy and lactation can shape offspring emotional development. It remains unclear whether isocaloric perinatal FRU exposure selectively alters distinct components of cocaine reinforcement, motivation, and reinstatement of cocaine-seeking behavior, and whether such effects are associated with mesostriatal receptor adaptations. Methods: Male and female Wistar rat offspring from dams fed a standard diet or an isocaloric FRU diet acquired intravenous cocaine self-administration (COC SA) under a stable fixed-ratio schedule of reinforcement across increasing doses (0.25-1.0 mg/kg/infusion), followed by a progressive-ratio (PR) test, extinction, and cue- and cocaine-induced reinstatement. Based on these behavioral findings, synaptosomal melanocortin-4 receptor (MC4R) and dopamine D1/D2 receptors (DRD1/DRD2) were assessed in the nucleus accumbens (NAc) and dorsal striatum (dSTR) of male offspring, in both cocaine-naïve and cocaine-experienced animals. Results: Maternal FRU exposure produced sex-, dose-, and phase-dependent shifts in the session-dependent patterns of cocaine responding, without increasing cumulative cocaine intake. Notably, FRU-exposed males exhibited a lower PR breakpoint, indicating reduced effort-based motivation for cocaine. Extinction learning was preserved in both sexes, although maternal FRU exposure influenced the rate of response decline across sessions. Cue- and cocaine-induced reinstatements were not significantly altered by maternal diet. In cocaine-naïve males, maternal FRU exposure was associated with reduced DRD1 and increased MC4R in both regions, with no change in DRD2. Following COC SA and reinstatement, FRU-exposed males exhibited reduced DRD2 and a lower DRD2/DRD1 ratio in both regions, accompanied by a selective reduction of MC4R in dSTR. Conclusion: Together, these findings indicate that maternal isocaloric FRU exposure selectively shapes the motivational organization of COC SA, most evident under high-effort conditions, without altering reinstatement behavior, and is accompanied by experience-dependent remodeling of mesostriatal dopaminergic and melanocortin receptor profiles in male offspring. (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare no relevant financial or non-financial conflicts of interest. |
| Contributed Indexing: | Keywords: Cocaine self-administration; Dopamine receptors; Fructose; Maternal diet; Melanocortin-4 receptor; Motivation |
| Substance Nomenclature: | I5Y540LHVR (Cocaine) 30237-26-4 (Fructose) 0 (Receptors, Dopamine D2) 0 (Receptor, Melanocortin, Type 4) 0 (Dopamine Uptake Inhibitors) 0 (Receptors, Dopamine D1) 0 (melanocortin receptor type 4, rat) |
| Entry Date(s): | Date Created: 20260416 Date Completed: 20260715 Latest Revision: 20260715 |
| Update Code: | 20260715 |
| DOI: | 10.1016/j.bbr.2026.116222 |
| PMID: | 41991004 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-7549 |
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| DOI: | 10.1016/j.bbr.2026.116222 |