Synaptic Depression Via Mglur1 Positive Allosteric Modulation Suppresses Cue-Induced Cocaine Craving

Cue-induced cocaine craving is a major cause of relapse in abstinent addicts. In rats, cue-induced craving progressively intensifies (incubates) during withdrawal from extended-access cocaine self-administration. After ~1 month of withdrawal, incubated craving is mediated by Ca(2+)-permeable AMPA receptors (CP-AMPARs) that accumulate in the nucleus accumbens (NAc). We found that decreased mGluR1 surface expression in the NAc preceded and enabled CP-AMPAR accumulation. Thus, restoring mGluR1 transmission by administering repeated injections of an mGluR1 positive allosteric modulator (PAM) prevented CP-AMPAR accumulation and incubation, whereas blocking mGluR1 transmission at even earlier withdrawal times accelerated CP-AMPAR accumulation. In studies conducted after prolonged withdrawal, when CP-AMPAR levels and cue-induced craving are high, we found that systemic administration of an mGluR1 PAM attenuated the expression of incubated craving by reducing CP-AMPAR transmission in the NAc to control levels. These results suggest a strategy in which recovering addicts could use a systemically active compound to protect against cue-induced relapse

Unilateral Diaphragmatic Paralysis in a Diabetic Patient: A Case of Trepopnea

Dyspnea is a common presenting complaint. Trepopnea, an under-recognized form of dyspnea, is difficult breathing in only one lateral decubitus position. One cause of trepopnea is unilateral diaphragmatic paralysis, which in itself is an uncommon diagnosis. We report a unique case of a 55-year-old diabetic man who presented with trepopnea and was found to have unilateral diaphragmatic paralysis secondary to isolated diabetic phrenic neuropathy. This case highlights the importance of recognizing trepopnea as an early clinical symptom of diaphragmatic paralysis and discusses diabetic phrenic neuropathy which can occur in the absence of peripheral neuropathy