Early adolescent nicotine exposure affects later-life hippocampal mu-opioid receptors activity and morphine reward but not physical dependence in male mice

Rationale: There is extensive literature regarding nicotine-opioid functional interactions. The possibility that use of nicotine products during adolescence might increase the risk of substance abuse such as morphine later in adulthood is particularly relevant to the current opioid crisis. Objectives: To investigate the effects of nicotine exposure for seven days during adolescence in mice on morphine reward as well as morphine physical dependence later in adulthood. Methods: Mice were exposed to nicotine in either early or late adolescence then evaluated for morphine reward and withdrawal symptoms in adulthood. A separate group of mice was exposed to nicotine during adolescent and tissue was evaluated for changes in MOR-mediated G-protein activity using [S-35]GTP gamma S binding assays. Results: We report that a 7-day exposure to a low dose of nicotine during early adolescence significantly enhanced morphine preference in the CPP test in adult mice. In contrast, the same treatment with nicotine had no effect on expression of somatic withdrawal signs in morphine-dependent adult mice. MOR-mediated G-protein activity in hippocampus, but not thalamus and striatum of adult mice, was significantly altered by adolescent nicotine treatment. Conclusions: Adolescence is a unique developmental stage during which nicotine has long-term effects on future drug-taking behavior. Further studies are needed to identify the neurotransmitters and mechanisms involved in increased vulnerability to drug abuse.