ResearchPod Summary
People with schizophrenia face exceptionally high rates of nicotine use, which complicates treatment and worsens health outcomes. Given that the mesolimbic dopamine system is central to both schizophrenia pathology and the rewarding effects of nicotine, this study investigated whether targeting the mGlu5 receptor—part of a complex that regulates dopamine signaling—could attenuate nicotine reward in a rodent model of psychosis.
The researchers used a well-established neonatal quinpirole (NQ) rat model, in which early-life exposure to the dopamine D2-like receptor agonist quinpirole leads to lifelong D2 receptor hypersensitivity, mimicking key features of schizophrenia. Adolescent rats underwent a conditioned place preference (CPP) paradigm to assess nicotine reward. The study tested the impact of the mGlu5 positive allosteric modulator (PAM), CDPPB, administered prior to nicotine exposure. Following behavioral testing, brain tissue from the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) was analyzed for markers of synaptic plasticity: BDNF, cadherin-13 (Cdh13), and phosphorylated p70S6K.
These findings suggest that mGlu5 receptors are a viable pharmacological target for managing comorbid nicotine use in psychosis. By modulating the plasticity associated with dopamine D2 supersensitivity, agents like CDPPB may help break the cycle of reward-learning that reinforces addiction in individuals with schizophrenia, providing a potential strategy to reduce both drug-seeking behaviors and the associated neurobiological vulnerabilities.
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