The effect of postretrieval extinction of nicotine pavlovian memories in rats trained to self-administer nicotine.

INTRODUCTION: Retrieval (reactivation) of smoking-related memories is a potent trigger of relapse among ex-smokers, and manipulation of smoking-related memories is considered to be a promising target for therapeutic intervention. Recent studies have shown that postreactivation extinction attenuates drug-related memories and relapse to drug-seeking both in rodents and in humans. We investigated the effect of postreactivation extinction in a rat model of relapse to nicotine-seeking. METHODS: Rats were trained to self-administer nicotine in context A (CxA). Pressing the active lever resulted in the nicotine infusion paired with a cue-light (CS). Nicotine-related Pavlovian memories were then reactivated via presentation of 3 non-contingent CS. We then extinguished nicotine-related memories in a distinct context (CxB) followed 24hr later by the assessment of renewal of responding in CxA. RESULTS: Postreactivation extinction, applied 1 but not 6hr after reactivation, induced a significant reduction of the rate of responding on renewal compared to responding during nicotine self-administration, whereas no such effect of CS-Extinction was observed in No-Reactivation group. However, between-group comparisons of responding during renewal did not show any significant difference. CONCLUSIONS: Current results show that the reactivation of nicotine-related Pavlovian memories may reduce the effect of renewal to exert nicotine-seeking. However, it appears that this effect is small in size and is not significantly different from CS-Extinction alone.

A novel process driving Alzheimer's disease validated in a mouse model: Therapeutic potential.

Introduction: The neuronal mechanism driving Alzheimer's disease (AD) is incompletely understood. Methods: Immunohistochemistry, pharmacology, biochemistry, and behavioral testing are employed in two pathological contexts-AD and a transgenic mouse model-to investigate T14, a 14mer peptide, as a key signaling molecule in the neuropathology. Results: T14 increases in AD brains as the disease progresses and is conspicuous in 5XFAD mice, where its immunoreactivity corresponds to that seen in AD: neurons immunoreactive for T14 in proximity to T14-immunoreactive plaques. NBP14 is a cyclized version of T14, which dose-dependently displaces binding of its linear counterpart to alpha-7 nicotinic receptors in AD brains. In 5XFAD mice, intranasal NBP14 for 14 weeks decreases brain amyloid and restores novel object recognition to that in wild-types. Discussion: These findings indicate that the T14 system, for which the signaling pathway is described here, contributes to the neuropathological process and that NBP14 warrants consideration for its therapeutic potential.