mise à jour du
30 octobre 2003
 Physiology & Behavior
1995; 57; 5; 881-885
Neuronal substrate of electrically induced grooming in the PVH of the rat: involvement of oxytocinergic systems?
AM. Von Erp, MR. Kruk, et al
Medical pharmacology, Sylvius laboratory, U of Leiden, Netherlands


Electrical stimulation of the hypothalamus induces distinct behavioural responses. Depending on the precise site of activation, different responses are evoked: for example, stimulation of the intermediate hypothalamic area (MA), situated between the lateral hypothalamus and ventromedial nucleus, may induce attack behaviour, and stimulation of the paraventricular area may induce self-grooming. Depending on the current intensity used, physical properties of the electrode, and physiological properties of the brain tissue, a larger or smaller population of neurons and/or fibres may be activated. Therefore, a detailed analysis of evoked behavioural responses has to be combined with precise histological verification, to identify the neuronal substrate that is activated during elicitation of a particular response. In the present report, the hypothalamic distribution data from several experiments, in which electrical stimulation was used to evoke grooming responses, have been pooled and their distribution reexamined. Some of these data have been published previously.
Grooming can also be induced by the intracerebroventricular administration of peptides, such as adrenocorticotrope hormone (ACTH), a-melanocyte-stimulating hormone (a-MSH), beta-endorphin, oxytocin, or bombesin. In previous reports we have shown that local injection of some of these peptides into or near the PVH also may induce grooming. Interestingly, we found that slow infusion of oxytocin into the PVH in resting animals, after they had settled down, induced grooming, whereas a-MSH had no effect at all . This suggests that oxytocin-receptive systems may be involved in the initiation of grooming. It has been described that, apart from the axons, the dendrites of the oxytocinergic cells in the PVH may release oxytocin as well. Therefore, we decided to compare the distribution of electrode sites at which grooming was induced with the general distribution of oxytocin-immunoreactive neurons and fibres in the PVH and rostral hypothalamus. [...]
The distribution of electrode sites at which grooming can be evoked with short latencies and at low threshold current intensity is concentrateil in the hypothalamic paraventricular area. This area coincides with previous observations. Moreover, it is very similar to the area where grooming could be elicited by microinjection of several neuroactive substances. No grooming responses can be evoked from other areas of the hypothalamus, as bas been shown in an extensive distribution study by Lammers et al.. The best responses are consistently obtained from the PVH (ie., for electrical stimulation: a threshold for grooming within 10 s determined in the first test; for peptide-induced grooming: grooming within 1 min after injection, accompanied by yawning and leading to a grooming score of more that 70% in the first 15 min after injection). In addition, grooming can be induced reliably from areas adjacent to the PVH: around the fornix, along the wall of the third ventricle, and in the anterior hypothalamic area. In these sites, grooming may be induced by activation of afferent or efferent pathways to the PVH.
There are many different peptides present in the PVH, of which several have been reported to be involved in the regulation of grooming, such as oxytocin, corticotropin-releasing hormone, ACTH, and a-MSH. However, there are differences in the grooming patterns induced by different manipulations. Grootning induced by electrical stimulation increases the frequency and duration of face washing and body grooming, at the expense of scratching. Grooming induced by oxytocin infusion into the PVH of resting rats also increases body groorning, but not face washing, at the expense of tail and paw grooming. Interestingly, we observed that at sites in the PVH yawning was often induced, after both electrical and mechanical stimulation. Yawning has been reported to occur after injection of oxytocin into the PVH. Direct microinjections into the PVH of low doses of excitatory amino acids (kainic acid, NMDA) or peptides (ACTH, a-MSH) also induce grooming. However, in a previous study we have shown that grooming induced by peptides like ACTH and a-MSH can be separated in two phases. The initiation of grooming may be the result of mechanical stimulation of the PVH and/or handling procedures, because saline injections have a similar effect. The administration of peptides leads to a considerable prolongation of these initial effects. Probably, the initiation phase is an effect of tissue compression or damage in or near the target area. This leads to the release of endogenous substances from damaged cells, which have an effect on neighbouring cells. It is known that damaged cells release large amounts of excitatory amino acids (EAAs). This might lead to the activation of the area surrounding the needle tip. Interestingly, slow infusion into the PVH via a remote control cannula system does not lead to a biphasic grooming effect. In a resting animal, a-MSH appears to be ineffective, whereas oxytocin infusion induces a clear-cut grooming response. This supports the suggestion that oxytocinergic systems are involved in PVH-induced grooming. Oxytocin infusions may activate oxytocinergic neurons via putative autoreceptors, whereas electrical stimulation may activate oxytocinergic neurons and fibres simultaneously.
In an extensive anatomical study, Roeling showed that pathways originating from the hypothalamic grooming area (HGA) are very similar to the oxytocinergic pathways in the brain, in contrast with projections from other neighbouring parts of the hypothalamus. One of the descending efferent pathways from the HGA runs via the ventral tegmental area (VTA) through the brainstem; another pathway runs via the periaqueductal gray (PAG) and central tegmental field. In a pilot study, we found that PAG lesions, completely interrupting the descending hypothalamic fibres, had no effect on grooming responses evoked by electrical stimulation of the HGA. This suggests that the major pathway involved in hypothalamic grooming runs ventrally via the VTA. Interestingly, injection of oxytocin into the VTA has been reported to induce grooming. Other findings support the suggestion that the VTA, which is one of the origins of the dopamine system, is more important for the execution of hypothalamic grooming than the opioid-rich PAG: the opiate antagonist naloxone does not inhibit electrically induced grooming, whereas the dopaminergic antagonist haloperidol does (Van Erp, unpublished data). Recently it has been confirmed that the PAG is important for ACTH-induced, but not oxytocin-induced, grooming.
We conclude that there are interesting similarities in the distribution of electrode sites at which grooming can be induced and oxytocinergic neurons and fibres in the hypothalamus. Together with anatomical, pharmacological, and lesion studies in and outside the hypothalamus, we hypothesize that electrical and mechanical stimulation of the hypothalamic grooming area-including the PVH and some closely surrounding parts of the rostral hypothalamus- initiates a direct grooming response, probably by involvement of oxytocinergic mechanisms. However, more research is needed to test this hypothesis (e.g., by applying oxytocin antagonists during PVH stimulation).