Induction of oral dyskinesias in naive rats by D1 stimulation

Rosengarten, H; Schweitzer, Jack W.; Friedhoff, Arnold J.

doi:10.1016/0024-3205(83)90155-8

Cited by 242 publications

(66 citation statements)

References 11 publications

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“…The increased mouth movements are used as an animal model of tardive dyskinesia (1,2). The increase in mouth movements is also induced by a single adminis tration of the selective dopamine Di-agonist SKF 38393 (3,4). The increased mouth movements of the rat in duced by the long-term administration of neuroleptics and that induced by the administration of the selective D,-agonist SKF 38393 resemble each other in the aspect that both are characterized by a relative excess of D, activity (3,4).…”

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“…The increase in mouth movements is also induced by a single adminis tration of the selective dopamine Di-agonist SKF 38393 (3,4). The increased mouth movements of the rat in duced by the long-term administration of neuroleptics and that induced by the administration of the selective D,-agonist SKF 38393 resemble each other in the aspect that both are characterized by a relative excess of D, activity (3,4). Cholecystokinin octapeptide (CCK-8) suppresses both SKF 38393-induced behavior and chron ic neuroleptic-induced involuntary dyskinetic disorders (2,5).…”

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Delayed Supprressive Effect of a Low Dose of Caerulein on the Grooming Behavior Induced by the D1-Receptor Agonist SKF 38393.

Masuda¹,

Murai²,

Saito³

et al. 1992

Jpn.J.Pharmacol

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ABSTRACT-Caerulein (CLN, 0.8-80,ug/kg, s.c.) was administered to male rats 10 min or 24 hr be fore the injection of SKF 38393 (3 mg/kg, i.p.). The increased mouth movement and grooming be havior by SKF 38393 were suppressed dose-dependently by CLN 10 min before the SKF 38393. CLN at the dose of 0.8 ,ug/kg, given 24 hr before the SKF 38393, suppressed the grooming behavior by SKF 38393. These findings suggest that a low dose of CLN, but not a high dose, had a delayed suppressive effect on the grooming behavior induced by an excess of D,-activity.Keywords: Caerulein, SKF 38393, Grooming behaviorLong-term administration of a neuroleptic to schizo phrenic patients can often result in involuntary dys kinetic disorders such as tardive dyskinesia, which is thought to be mediated by an increased dopaminergic activity in the striatum. Chronic treatment of rats with neuroleptics cause an increase in mouth movements. The increased mouth movements are used as an animal model of tardive dyskinesia (1, 2). The increase in mouth movements is also induced by a single adminis tration of the selective dopamine Di-agonist SKF 38393 (3, 4). The increased mouth movements of the rat in duced by the long-term administration of neuroleptics and that induced by the administration of the selective D,-agonist SKF 38393 resemble each other in the aspect that both are characterized by a relative excess of D, activity (3, 4). Cholecystokinin octapeptide (CCK-8) suppresses both SKF 38393-induced behavior and chron ic neuroleptic-induced involuntary dyskinetic disorders (2, 5). This suggests that CCK-8 may be of use against involuntary dyskinetic disorders. These studies were carried out with an emphasis on analyzing the immedi ate effect of CCK-8. Caerulein (CLN), an analogue of CCK-8, has a long lasting effect on the monoamine level in rat brain re gions (6). Behavioral studies showed the long-lasting effect of CLN (7,8). For example, Ogawa et al. (8) re ported long-lasting effect of CLN on permanent motor behavioral abnormalities induced by the neurotoxin iminodipropionitrile. Moreover, CLN produced biphasic and long-lasting improvement in a schizophrenic patient with bucco-lingual dyskinesia (9). These reports suggest that CLN has a continuous or delayed suppressive effect on involuntary movements. In this study, we de termined if CLN has a delayed suppressive effect on the mouth movements and grooming behavior induced by SKF 38393.Eighty male Sprague-Dawley rats (Nihon SLC, Shizu oka, Japan), initially weighing 250-300g, were housed three per cage on a 12-hr light -12-hr dark cycle and allowed standard food pellets and water ad libitum for one week before the experiment.To test the immediate effect of CLN, five rats were placed individually in transparent boxes (18 X 26 X 28 cm) and left there for one hour to acclimate them. Then CLN (ceruletide diethylamine, synthesized at the Shionogi Research Pharmaceuticals Laboratories) was subcutaneously administered in doses of 0.8, 8 and 80 ,ug/kg to the 1st, 2nd, and 3rd rat, respectively, and sa...

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Delayed Supprressive Effect of a Low Dose of Caerulein on the Grooming Behavior Induced by the D1-Receptor Agonist SKF 38393.

Masuda¹,

Murai²,

Saito³

et al. 1992

Jpn.J.Pharmacol

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“…Seeman, 1980). Studies employing recently developed selective D, and D, agonists and antagonists, however, have suggested that the D, receptor mediates some of the behavioral effects of dopaminergic drugs both in normal animals and in those with 6-OHDA or reset-pine-induced dopamine depletion (Rosengarten et al, 1983;Molloy and Waddington, 1984;Arnt, 1985;Braun and Chase, 1985;Breese et al, 1985a, b).…”

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Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions

Trugman¹,

Wooten²

1987

J. Neurosci.

153

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he relative roles of D1 and D2 dopamine receptor stimulation in mediating the antiparkinsonian effects of dopaminergic drugs remain unclear. To determine the functional metabolic consequences of selective dopamine receptor stimulation, we used 2-deoxyglucose (2-DG) autoradiography to examine the effects of the D1 agonist SKF-38393 and the D2 agonist LY-171555 on regional cerebral glucose utilization (RCGU) in rats with unilateral 6-hydroxydopamine (6-OHDA) substantia nigra lesions. SKF-38393 (0.5-25.0 mg/kg) and LY-171555 (0.01-5.0 mg/kg) produced indistinguishable behavioral responses, including vigorous contralateral rotation. Treatment with each drug similarly increased glucose utilization, dose-dependently, in the parafascicular thalamus, subthalamic nucleus, deep layers of the superior colliculus, and lateral midbrain reticular formation ipsilateral to the nigral lesion; glucose utilization was decreased in the ipsilateral lateral habenula. By contrast, the D1 and D2 agonists differentially altered glucose utilization in the entopeduncular nucleus (EP) and the substantia nigra pars reticulata (SNr). SKF-38393, 5.0 and 25.0 mg/kg, increased glucose utilization 127 and 275%, respectively, in the pars reticulata ipsilateral to the lesion. LY-171555, 1.0 and 5.0 mg/kg, caused maximal contralateral turning, yet did not alter glucose utilization in the ipsilateral SNr. The glucose utilization response of the ipsilateral EP paralleled that of the SNr demonstrating large increases following administration of SKF-38393 and minimal change following the use of LY-171555. The results demonstrate that the selective D1 agonist reproduces the marked glucose utilization increases (2-3-fold above control values) in the EP and SNr that were previously observed using L-DOPA and apomorphine in this model, whereas the selective D2 agonist does not.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Considerable correlative data attributes most of the physiological, behavioral, and clinical effects of DA neurotransmission to the D-2 receptor whereas, to date, there is considerably less evidence for a role for D-1 receptors within the CNS (Calne, 1980;Seeman, 1980). However, several recent reports have suggested possible behavioral correlates of D-l receptor activation, including rotational responses in rats with unilateral nigral lesions (Amt and Hytell, 1984;Gershanik et al, 1983;Gower and Marriott, 1982;Setler et al, 1978), specific grooming responses (Molloy and Waddington, 1984) and oral dyskinesias (Rosengarten et al, 1983). In addition, one study has reported that D-1 receptor coupling to the adenylate cyclase may be more efficient in schizophrenics (Memo et al, 1983) suggesting that D-1 receptors may play a role in this disorder.…”

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Electrophysiological evidence for the existence of both D-1 and D-2 dopamine receptors in the rat nucleus accumbens

Fj¹,

Ry²

1986

J. Neurosci.

190

101

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Extracellular single-unit recording and microiontophoretic techniques were used to characterize the pharmacological properties of dopamine (DA) receptors within the rat nucleus accumbens (NAc), a forebrain structure that receives a dense innervation from mesolimbic DA-containing neurons (A10 DA neurons) located in the ventral tegmental area (VTA). Of the NAc neurons tested, 75% were inhibited by microiontophoretic administration of the selective D-2 receptor agonist, LY-141865, whereas 38% were inhibited by microiontophoretic administration of the selective D-l receptor agonist, SKF-38393. Of the 30 NAc neurons that were tested with both of these agonists, nine were inhibited by both agonists, 11 were inhibited only by LY-141865, five were inhibited only by SKF-38393, and five were not affected by either of these compounds. The inhibitory effects of LY-141865 were blocked and reversed by either intravenous or iontophoretic administration of the selective D-2 antagonist (-)-sulpiride, which, however, failed to alter the inhibitory effects of SKF-38393. In contrast, the purportedly selective D-l antagonist, SCH-23390, selectively blocked and reversed the inhibitory effects of SKF-38393, suggesting that the two agonists were producing their inhibitory effects via distinct DA receptors. Additional experiments indicated that intravenous administration of LY-141865 caused a biphasic increase/decrease in the activity of NAc neurons. The initial rate increase was apparently due to disinhibition since it was also shown that D-2 DA receptors located on A10 DA neurons exhibited a 3-lo-fold greater sensitivity to LY-141865 and DA as compared to the NAc D-2 receptors. These results suggest that both D-l and D-2 DA receptors exist within the NAc and that agonist occupancy of each of these receptors results in an inhibition of the activity of NAc neurons.The most widely accepted classification scheme for CNS dopamine (DA) receptors suggests the existence of two distinct receptor subtypes, labeled D-l and D-2 (Creese et al., 1983; Kebabian and Calne, 1979) which were originally defined on the basis of a stimulatory association with a DA-sensitive ad-

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Induction of oral dyskinesias in naive rats by D1 stimulation

Cited by 242 publications

References 11 publications

Delayed Supprressive Effect of a Low Dose of Caerulein on the Grooming Behavior Induced by the D1-Receptor Agonist SKF 38393.

Delayed Supprressive Effect of a Low Dose of Caerulein on the Grooming Behavior Induced by the D1-Receptor Agonist SKF 38393.

Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions

Electrophysiological evidence for the existence of both D-1 and D-2 dopamine receptors in the rat nucleus accumbens

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