Age-dependent memory impairment induced by co-exposure to nicotine and a synthetic cannabinoid in mice

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2023-12, Vol.127, p.110821-110821, Article 110821
• Main Authors: Gonçalves, Patricia Felix Rolo, Nunes, Luis Eduardo Duarte, Andrade, Brenda da Silva, Silva, Mariana Oliveira Lopes da, Souza, Isis Nem de Oliveira, Assunção-Miranda, Iranaia, Castro, Newton Gonçalves, Neves, Gilda Angela
• Format: Article
• Language: English
• Subjects: Critical periods; Drug abuse; Drug interaction; Drug withdrawal; Neurodevelopment; Recognition memory
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2023.110821

Co-use of marijuana and tobacco products is the second most common drug combination among adolescents. Nicotine (NIC) and cannabinoid use during adolescence induce similar detrimental changes, raising the hypothesis that simultaneous exposure could result in even more severe outcomes. Thus, we investigated whether the co-exposure to NIC and the synthetic cannabinoid WIN 55,212–2 (WIN) in adolescent mice causes behavioral outcomes different from those observed after exposure to a single drug. Male Swiss mice were exposed twice daily to NIC, WIN, or NIC + WIN during adolescence (PND28–47) or adulthood (PND70–89). Drug combination led to a greater reduction in weight gain in adolescent mice, while NIC-induced weight loss was observed in adults. During administration, NIC provoked hypothermia, and WIN produced hyperlocomotion in adolescent and adult mice. Animals exposed to NIC + WIN presented a profile of changes similar to those exposed to NIC. After drug exposure, changes in locomotion, thigmotaxis, social preference, prepulse inhibition, and working and recognition memory were evaluated. Adolescent but not adult mice exposed to NIC showed withdrawal-related hyperlocomotion unaffected by WIN co-administration. An age-specific impairment in object recognition memory was induced only by drug co-exposure during adolescence, which resolved spontaneously before reaching early adulthood. A transient decrease in hippocampal α7 nAChR subunit and CB1 receptor mRNA levels was induced by NIC exposure, which may be involved but is not enough to explain the memory impairment. Our work confirms the potential of NIC and cannabinoids association to aggravate some of the individual drug effects during critical neurodevelopmental periods. [Display omitted] •Age of exposure determines the behavioral outcomes of nicotine + WIN 55,212–2.•In adolescent mice, nicotine + WIN 55,212–2 causes short-term memory impairment.•Nicotine withdrawal induces hyperlocomotion not affected by WIN 55,212–2.•In adult mice, nicotine + WIN 55,212–2 does not cause lasting behavioral changes.•Nicotine withdrawal reduces hippocampal α7 nicotinic and CB1 receptor mRNA levels.