THE NEUROPHARMACOLOGY OF YAWNING

Yawning is a phylogenetically old, stereotyped event that occurs alone or associated with stretching and/or penile erection in humans and in animals from reptiles to birds and mammals under different conditions . Although its physiological function is still unknown, yawning is und er the control of several neurotransmitters and neuropeptides at the c entral level as this short overview of the literature on the neurochem istry of yawning shows. Among these substances, the best known are dop amine, excitatory amino acids, acetylcholine, serotonin, nitric oxide, adrenocorticotropic hormone-related peptides and oxytocin, that facil itate yawning and opioid peptides that inhibit this behavioral respons e. Some of the above compounds interact in the paraventricular nucleus of the hypothalamus to control yawning. This hypothalamic nucleus con tains the cell bodies of oxytocinergic neurons projecting to extra-hyp othalamic brain areas that play a key role in the expression of this b ehavioral event. When activated by dopamine, excitatory amino acids an d oxytocin itself, these neurons facilitate yawning by releasing oxyto cin at sites distant form the paraventricular nucleus, i.e. the hippoc ampus, the pens and/or the medulla oblongata. Conversely, activation o f these neurons by dopamine, oxytocin or excitatory aminoacids, is ant agonized by opioid peptides, that, in turn, prevent the yawning respon se. The activation and inhibition, respectively of these oxytocinergic neurons is related to a concomitant increase and decrease, respective ly, of paraventricular nitric oxide synthase activity. However, other neuronal systems in addition to the central paraventricular oxytociner gic neurons are involved in the control of yawning, since they do not seem to be involved in the expression of yawning induced by the stimul ation of acetylcholine or serotoninergic receptors, nor by adrenocorti cotropic hormone (ACTH) and related peptides. Nitric oxide is also inv olved in the induction of yawning by the latter compounds and neuronal links, for instance between dopamine and acetylcholine and dopamine a nd serotonin, seem to be involved in the yawning response. Finally, ot her neurotransmitters, i.e. gamma-aminobutyric acid (GABA) and noradre naline, and neuropeptides, i.e. neurotensin and luteinizing hormone-re leasing hormone (LH-RH), influence this behavioral response. In conclu sion, in spite of some recent progress, little is known of, and more h as to be done to identify, the neurochemical mechanisms underlying yaw ning at the central level. (C) 1998 Elsevier Science B.V.