Intrapallidal administration of 6-hydroxydopamine mimics in large part the electrophysiological and behavioral consequences of major dopamine depletion in the rat.

In addition to GABA and glutamate innervations, the globus pallidus (GP) receives dopamine afferents from the pars compacta of the substantia nigra (SNc), and in turn, sends inhibitory GABAergic efferents to the subthalamic nucleus (STN) and the pars reticulata of the substantia nigra (SNr). Nevertheless, the role of dopamine in the modulation of these pallido-subthalamic and pallido-nigral projections is not known. The present study aimed to investigate the effects of intrapallidal injection of 6-hydroxydopamine (6-OHDA) on the electrical activity of STN and SNr neurons using in vivo extracellular single unit recordings in the rat and on motor behaviors, using the "open field" actimeter and the stepping test. We show that intrapallidal injection of 6-OHDA significantly decreased locomotor activity and contralateral paw use. Electrophysiological recordings show that 6-OHDA injection into GP significantly increased the number of bursty cells in the STN without changing the firing rate, while in the SNr neuronal firing rate decreased and the proportion of irregular cells increased. Our data provide evidence that intrapallidal injection of 6-OHDA resulted in motor deficits paralleled by changes in the firing activity of STN and SNr neurons, which mimic in large part those obtained after major dopamine depletion in the classical rat model of Parkinson's disease. They support the assumption that in addition to its action in the striatum, dopamine mediates its regulatory function at various levels of the basal ganglia circuitry, including the GP.

Role of the pineal gland and melatonin in the photoperiodic control of hypothalamic gonadotropin-releasing hormone in the male jerboa (Jaculus orientalis), a desert rodent.

The neuroendocrine mechanism underlying seasonal changes in gonadal activity of the jerboa, a desert hibernating rodent adapted to harsh climatic conditions, are poorly understood. We investigated the role of the pineal gland and melatonin in the photoperiodic control of hypothalamic gonadotropin-releasing hormone (GnRH). Intact and pinealectomized male jerboas were subjected to short photoperiod, while others were kept under long photoperiod and injected daily with melatonin or vehicle. Testes activity was monitored by evaluating the testes volume during 10 weeks. GnRH immunoreactivity was investigated quantitatively with image analysis. Following melatonin administration, the hormone peaked in plasma after 30 min, with return to control levels 2.5 h later. Exposure to short photoperiod and melatonin resulted in marked increase in the number of GnRH-containing cells in the preoptic area and mediobasal hypothalamus, whereas GnRH immunoreactivity of fibers and terminals in the median eminence decreased under these conditions. The findings indicate that in the jerboa short photoperiod induces testicular regression by prolonging the duration of melatonin as an endocrine signal. This mechanism probably involves inhibition of GnRH release in the median eminence, with consequent accumulation of GnRH in perikarya of the preoptic area and mediobasal hypothalamus. Interestingly, GnRH cells of the median eminence did not appear to be influenced by the photoperiod and pineal melatonin, whereas their number was increased by exogenous melatonin. The latter data suggest for the first time the involvement of an extrapineal melatonin, whose origin remains to be identified, in the modulation of the GnRH regulatory system in rodents.

Phytotherapy of hypertension and diabetes in oriental Morocco.

In order to select the main medicinal plants used in folk medicine to treat arterial hypertension and/or diabetes, a survey was undertaken in different areas of oriental Morocco. The patients (370 women and 256 men) were divided into three groups: diabetics (61%), hypertensives (23%) and hypertensive diabetic persons (16%). On average, 67.51% of patients regularly use medicinal plants. This proportion is perceptibly the same in all groups and does not depend on sex, age and socio-cultural level. This result shows that phytotherapy is widely adopted in northeastern Morocco. For diabetes, 41 plants were cited, of which the most used were Trigonella foenum-graecum L. (Leguminosae), Globularia alypum L. (Globulariaceae), Artemisia herba-alba Asso. (Compositae), Citrullus colocynthis (L.) Schrad. (Cucurbitaceae) and Tetraclinis articulata Benth. (Cupressaceae). In the hypertension's therapy 18 vegetal species were reported, of which the most used were Allium sativum L. (Liliaceae), Olea europea L. (Oleaceae), Arbutus unedo L. (Ericaceae), Urtica dioica L. (Urticaceae) and Petroselinum crispum A.W. Hill (Apiaceae). Among the 18 species used for hypertension, 14 were also employed for diabetes. Moreover, these two diseases were associated in 41% of hypertensives. These findings suggest that hypertension observed in this region would be in a large part related to diabetes.

[Proprioceptive and cutaneous evoked somatosensory potentials in the baboon: cycles of GABAergic excitability and inhibition]. / Potentiels évoqués somesthésiques proprioceptifs et cutanés chez le babouin: cycles d'excitabilité et inhibitions GABAergiques.

Double stimulations induce deep and long-lasting inhibition (0-300 ms) of the P16-N30 components of somatosensory potentials (SEP) evoked by sciatic or sural nerve stimulation. This inhibition is evidenced on both S1 and M1 cortical areas, demonstrating similar course and duration, whatever the source (right or left limb) and/or the modality (extero- or proprioceptive) of conditioning and testing afferences. The depth of this inhibition depends on the relative amplitude of the conditioning to testing SEP. After muscle injection of a subconvulsive dose of bicuculline, tSEPs are facilitated when individually elicited. When double stimulations are used, the inhibition of the SEP test is sharply reduced (with a 30-ms interstimulus delay). However, disinhibition of the conditioned SEP does not depend on separate individual SEP facilitations. Cortical GABAergic type a circuits are likely to be involved in inhibition of the conditioned SEP. This inhibition would be a non-invasive image of inhibitions that preserve the specificities of sensory messages in primary areas.

Synaptic inputs of tachykinin-containing nerve terminals to target tyrosine-hydroxylase-, beta-endorphin- and neuropeptide Y-producing neurons of the arcuate nucleus. Double pre-embedding immunocytochemical study in the rat.

Anatomical connections between tachykinin-containing terminals and three neuronal populations of the arcuate nucleus, chemically defined respectively by beta-endorphin (beta-END), tyrosine-hydroxylase or neuropeptide Y (NPY) and well represented in the arcuate nucleus, were studied using electron microscope double pre-embedding immunocytochemistry involving a combination of two sensitive chromogens: diaminobenzidine and tetramethylbenzidine. Following tachykinin immunodetection by diaminobenzidine, and tyrosine-hydroxylase, beta-END or NPY immunolabelling by tetramethylbenzidine, tachykinin-immunoreactive terminals were seen presynaptic to tyrosine-hydroxylase immunopositive cells and dendrites principally in the dorsomedial portion of the arcuate nucleus. Tachykinin-immunoreactive processes were also seen in synaptic contact with ventrolaterally located beta-END immunopositive perikarya. Tachykinin-immunopositive terminals also contacted NPY-immunoreactive cells and dendritic processes ventromedially. These results demonstrate the existence of a direct tachykinergic input onto three neuronal populations expected to play a role in the control of reproductive events. Consequently, they suggest, at least, an indirect action for tachykinins in the regulation of reproduction. Especially, tachykinins may indirectly control the luteinizing hormone-releasing hormone neurons via dopamine, beta-END and NPY cells and thereby influence luteinizing hormone secretion.

Direct and indirect enkephalinergic synaptic inputs to the rat arcuate nucleus studied by combination of retrograde tracing and immunocytochemistry.

The origin of both direct and indirect enkephalinergic innervation potentially able to influence neurons of the rat arcuate nucleus has been investigated by combining enkephalin immunocytochemistry and retrograde axonal transport of a wheatgerm agglutinin-Apo horseradish peroxidase-gold complex. Twenty four hours after tissue injections of small volumes (20 nl) of the tracer into the arcuate nucleus, rats were treated with colchicine and killed. In order to localize the enkephalinergic cells which directly innervate the arcuate nucleus, Vibratome sections were first silver-stained for detection of the wheatgerm agglutinin-Apohorseradish peroxidase-gold complex and then processed for enkephalin immunohistochemistry. To study the indirect enkephalinergic input to the arcuate nucleus, an electron microscope detection of immunoreactive synapses was carried out in areas rich in retrogradely labeled perikarya. Perikarya both immunoreactive and retrogradely labeled were observed ipsilaterally to the injection site in telencephalic structures such as the bed nucleus of the stria terminalis, medial preoptic and adjacent periventricular areas. Hypothalamic ipsilateral doubly labeled cells were localized principally in the dorsomedial nucleus and rostral arcuate nucleus. The major direct inputs arising from brainstem structures concerns the dorsal and ventral parabrachial nuclei. Moreover, at the ultrastructural level, numerous enkephalinergic terminals were demonstrated to synapse with retrogradely labeled perikarya and dendrites localized in the medial preoptic area, the hypothalamic paraventricular nucleus and the parabrachial nuclei providing evidence for an important enkephalinergic input on neurons projecting to the arcuate nucleus. Taken together, our light and electron microscope studies strongly suggest that the arcuate nucleus is the target of an enkephalinergic control originating from several regions and acting either directly or indirectly on neurons projecting to the arcuate nucleus.

Tachykinergic afferents to the rat arcuate nucleus. A combined immunohistochemical and retrograde tracing study.

The location of the cells giving rise to the tachykinergic innervation of the rat arcuate nucleus was studied by combining immunohistochemistry and retrograde axonal transport of a protein-gold complex (WGA-ApoHRP-gold). Small volumes (20 nl) of this marker were injected into the arcuate nucleus of the rat. Twenty-four to 30 h later, rats were injected with colchicine. After 24-h survival time, the paraformaldehyde-fixed brains were investigated for silver intensification of the gold particles and for tachykinin immunohistochemistry. Doubly immuno-silver-labeled cells were observed mainly in brainstem structures such as raphe nuclei, central gray pontine, and laterodorsal tegmental nucleus. Intranuclear and intrahypothalamic (ventromedial, dorsomedial, premamillary, and supramamillary) cell bodies were also doubly labeled, principally ipsilateral to the injection site. Minor afferent projections arise from the medial preoptic area. This anatomohistochemical study demonstrates that the arcuate nucleus receives intra- and extrahypothalamic tachykinergic inputs and shows that infundibular neurons undergo convergent tachykinergic influences.