Cancelling discrete and stopping ongoing rhythmic movements: Do they involve the same process of motor inhibition?

Motor inhibition is considered to be an important process of executive control and to be implicated in numerous activities in order to cancel prepared actions and, supposedly, to suppress ongoing ones. Usually, it is evaluated using a "stop-signal task" in which participants have to inhibit prepared discrete movements. However, it is unknown whether other movement types involve the same inhibition process. We therefore investigated whether the inhibition process for discrete movements is involved in stopping ongoing rhythmic movements as well. Twenty healthy adults performed two counterbalanced tasks. The first task was used to estimate the stop-signal reaction time (SSRTd) needed to inhibit prepared discrete key-pressing movements. In the second task, participants drew graphic patterns on a tablet and had to stop the movement when a stop-signal occurred. We calculated the rhythmic stop signal-reaction time as the time needed to initiate stopping such ongoing rhythmic movement (SSRTr) and the same latency relative to the period of the rhythmic movement (relSSRTr). We measured these delays under different movement frequencies and motor coordination conditions and further investigated whether they varied as a function of several parameters of the rhythmic movements (speed, mean and variance of the relative phase, and movement phase at several time events). We found no correlation between inhibition measures in the two tasks. In contrast, generalized linear models showed a moderate yet significant influence of the motion parameters on the inhibition of ongoing rhythmic movements. We therefore conclude that the motor inhibition processes involved in cancelling prepared discrete movements and stopping ongoing rhythmic movements are dissimilar.

Remifentanil produces cross-desensitization and tolerance with morphine on the mu-opioid receptor.

Remifentanil is a powerful mu-opioid (MOP) receptor agonist used in anaesthesia with a very short half-life. However, per-operative perfusion of remifentanil was shown to increase morphine consumption during post-operative period to relieve pain. In the present study, we aimed to describe the cellular mechanisms responsible for this apparent reduction of morphine efficacy. For this purpose, we first examined the pharmacological properties of both remifentanil and morphine at the MOP receptor, endogenously expressed in the human neuroblastoma SH-SY5Y cell line, to regulate adenylyl cyclase and the MAP kinase ERK1/2 pathway, their potency to promote MOP receptor phosphorylation, arrestin 3-CFP (cyan fluorescent protein) recruitment and receptor trafficking during acute and sustained exposure. In the second part of this work, we studied the effects of a prior exposure of remifentanil on morphine-induced inhibition of cAMP accumulation, activation of ERK1/2 and analgesia. We showed that sustained exposure to remifentanil promoted a rapid desensitization of opioid receptors on both signalling pathways and a pretreatment with this agonist reduced signal transduction produced by a second challenge with morphine. While both opioid agonists promoted Ser(375) phosphorylation on MOP receptor, remifentanil induced a rapid internalization of opioid receptors compared to morphine but without detectable arrestin 3-CFP translocation to the plasma membrane in our experimental conditions. Lastly, a cross-tolerance between remifentanil and morphine was observed in mice using the hot plate test. Our in vitro and in vivo data thus demonstrated that remifentanil produced a rapid desensitization and internalization of the MOP receptor that would reduce the anti-nociceptive effects of morphine.