Biomedical subjects

D P Gaudin

Publications and source records attributed to D P Gaudin.

5 recordsLinked to original sources

PubMed1994

Transsynaptic effect of an intrastriatal fetal nigral graft on the sensitivity of the substantia nigra pars reticulata to muscimol in the rat.

In the present study, we have investigated the effect of a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway and of a fetal nigral graft in the striatum on circling induced by unilateral microinjection of muscimol in a target structure of the striatum, the substantia nigra pars reticulata. A group of ovariectomized female rats received a unilateral nigral lesion with 6-hydroxydopamine. The lesioned animals were then tested for apomorphine circling (0.25 mg/kg sc). The animals which displayed circling with this drug were divided into two groups with equivalent circling rate. One group received a graft of 1.5 x 10(6) cells taken from the ventral mesencephalon of 14- to 15-day-old rat embryos and the other was kept as control. Six months after the graft, all animals received one microinjection on each side of the GABAergic agonist muscimol (25 ng/0.5 microliters) in site A (rostral part) or in site B (caudal part) of the substantia nigra pars reticulata using indwelling guide cannulae. Circling was monitored during 90 min after the injection. Our results show that: (1) Unilateral degeneration of the nigrostriatal pathway was associated with a decrease of contralateral rotation when muscimol was injected in site A (rostral part) and an increase when administrated in site B (caudal part) of the substantia nigra pars reticulata on the lesioned side compared to the intact side. (2) A fetal nigral graft implanted into the striatum can normalize the changes in GABAergic sensitivity in site A but not in site B of the substantia nigra pars reticulata.

Animals↗

PubMed1993

A fetal nigral graft prevents behavioral supersensitivity associated with repeated injections of L-dopa in 6-OHDA rats. Correlation with D1 and D2 receptors.

The effect of repeated administration of L-3,4-dihydroxyphenylalanine was studied behaviorally and biochemically in grafted versus non-grafted rats with a 6-hydroxydopamine unilateral lesion of the dopaminergic nigro-striatal pathway. Non-grafted rats receiving 14 injections of L-3,4-dihydroxyphenylalanine increased their contraversive circling while grafted rats did not, even after fourteen injections. The density of striatal dopamine receptors was examined by autoradiography using the ligands [3H]-SCH 23390 for dopamine D1 receptors and [3H]-spiperone for D2 receptors. In rats with a lesion of the nigro-striatal dopaminergic pathway, an increase of [3H]-SCH 23390 and [3H]-spiperone binding in the lesioned striatum was observed when compared with the striatum on the intact side. Chronic treatment with L-3,4-dihydroxyphenylalanine led to a further increase in D1 receptor density in the lesioned as well as the intact side. A similar pattern was observed for D2 receptors although the change did not reach significance. A graft of fetal nigral neurons brought the density of both D1 and D2 receptors on the lesioned side back to the level of the intact side. This is observed both in acutely or chronically L-3,4-dihydroxyphenylalanine treated rats. This study suggests that nigral grafts protect the striatum against L-3,4-dihydroxyphenylalanine-induced supersensitivity. It appears that the graft preserves the symmetry of the striatum even though there is an increase of D1 dopamine receptors. These results suggest that a fetal nigral graft could prevent the induction of 3-4-dihydroxyphenylalanine- induced dyskinesia in parkinsonian patients.

Animals↗

PubMed1991

Correlation of functional recovery after a 6-hydroxydopamine lesion with survival of grafted fetal neurons and release of dopamine in the striatum of the rat.

Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least two weeks later they were tested with amphetamine (5 mg/kg, s.c.) and apomorphine (0.25 mg/kg, s.c.). A cell suspension from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. The amphetamine test was then repeated every month for six months. The pattern of circling to amphetamine before the graft was strictly ipsiversive in all animals. From the first month we observed a progressive change and three patterns of rotation could be observed. In 21% of animals, the total number of ipsiversive turns in 90 min actually increased but during the first 20 min the animals turned contralaterally to the lesion (and to the graft). In 38% of animals, the total number of turns switched from ipsiversive to contraversive with the animals turning initially toward the intact side and during the second half of the test toward the lesion. Finally 41% of rats progressively switched to turning only toward the intact side. In all cases, maximal contraversive turning occurred during the initial 20 min. In these rats, tyrosine hydroxylase-positive cells were detected mainly in the dorsal striatum with a few in the central portion. Moreover there was a strong correlation between the number of surviving grafted neurons and the growth of their fiber into the host striatum and the extent of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

PubMed1991

Decrease of behavioral and biochemical denervation supersensitivity of rat striatum by nigral transplants.

The effect of fetal mesencephalic transplants on dopamine receptor supersensitivity has been studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least one month later they were tested with apomorphine (0.25 mg/kg, s.c.), amphetamine (5 mg/kg, s.c.), LY 171555 (D2 agonist) (0.5 mg/kg, i.p.) and CY 208243 (D1 agonist) (0.5 mg/kg, s.c.). A suspension containing approximately 1.5 x 10(6) cells from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. Six months later, grafted dopamine neurons reinnervated the medial part of the dorsal striatum, increased the dopamine level and reversed the rotational asymmetry evoked by amphetamine. Apomorphine given four months post-transplant still elicited contraversive circling but the number of turns was reduced. Circling evoked six months post-transplant by CY 208243 or LY 171555 was significantly less in grafted rats than in lesioned non-grafted rats. The density of dopaminergic receptors in the striatum of grafted and lesioned rats was examined by autoradiography by means of in vitro binding with [3H]SCH 23390 for D1 receptors and [3H] spiperone for D2 receptors. The results show that intrastriatal nigral transplants decrease the supersensitivity of the D2 receptors and to a lesser extent of the D1 receptors. Normalization of D2 receptors may explain the decrease of behavioral supersensitivity following administration of apomorphine and D2 agonist in grafted rats. D1 receptors were less affected by the lesion and also less normalized than D2 receptors by the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Fetal dopamine neuron transplants prevent behavioral supersensitivity induced by repeated administration of L-dopa in the rat.

We have studied in adult rats bearing a unilateral nigral lesion the effect of nigral grafts into the striatum on behavioral supersensitivity induced by chronic treatment of L-DOPA (100 mg/kg i.p.) plus benserazide (50 mg/kg i.p.). Repeated administration of L-DOPA increases contraversive circling. In rats without graft the contraversive circling was significantly increased after 8 and 14 daily injections of L-DOPA. On the other hand, the animals with transplants showed no such increase. Behavioral supersensitivity induced by repeated treatment of L-DOPA is often correlated with dyskinesia observed in the Parkinsonian patients. This suggests that the graft might be able to prevent this secondary effect.

Animals↗