Deletion of guanine nucleotide binding protein alpha z subunit in mice induces a gene dose dependent tolerance to morphine.

The mechanism underlying the development of tolerance to morphine is still incompletely understood. Morphine binds to opioid receptors, which in turn activates downstream second messenger cascades through heterotrimeric guanine nucleotide binding proteins (G proteins). In this paper, we show that G(z), a member of the inhibitory G protein family, plays an important role in mediating the analgesic and lethality effects of morphine after tolerance development.

Preoptic hypothalamic warming suppresses laryngeal dilator activity during sleep.

Upper airway dilator activity during sleep appears to be diminished under conditions of enhanced sleep propensity, such as after sleep deprivation, leading to worsening of obstructive sleep apnea (OSA). Non-rapid eye movement (NREM) sleep propensity originates in sleep-active neurons of the preoptic area (POA) of the hypothalamus and is facilitated by activation of POA warm-sensitive neurons (WSNs). We hypothesized that activation of WSNs by local POA warming would inhibit activity of the posterior cricoarytenoid (PCA) muscle, an airway dilator, during NREM sleep.

Diaphragm plasticity following intrinsic laryngeal muscle denervation in rats.

Purpose: During inspiration, recruitment of the intrinsic laryngeal muscles (ILM) reduces the inspiratory load on the ventilatory pump muscles. The purpose of our study was to determine 1) whether the diaphragm adapts to denervation of the ILM, and 2) whether the additional stimulus of exercise training affects the degree to which the diaphragm adapts to ILM denervation.

Methods: Thirty-six male Sprague-Dawley rats (2 months) were randomly divided into sedentary control (SC), sedentary-denervated (SD), and exercise-denervated (ED) groups.

Hypertolerance to morphine in G(z alpha)-deficient mice.

Our laboratory has generated a mouse deficient in the alpha (alpha) subunit of the G protein, G(z), (G(z alpha)) gene and we have examined the involvement of G(z alpha) in spinal and supraspinal analgesia and tolerance mechanisms. Spinal analgesia was tested by the response times to heat or cold tail flick times in a water bath at 50 degrees C or -5 degrees C and supraspinal analgesia was tested by the times for paw licking and jumping from a plate at 52 degrees C or 0.5 degrees C.