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At least 919 records · Page 51Linked to original sources
PubMed2004

Lesion of subthalamic or motor thalamic nucleus in 6-hydroxydopamine-treated rats: effects on striatal glutamate and apomorphine-induced contralateral rotations.

A unilateral lesion of the rat nigrostriatal pathway with 6-hydroxydopamine (6-OHDA) results in a decrease in the basal extracellular level of striatal glutamate, a nearly complete loss of tyrosine hydroxylase (TH) immunolabeling, an increase in the density of glutamate immunogold labeling within nerve terminals making an asymmetrical synaptic contact, and an increase in the number of apomorphine-induced contralateral rotations. [Meshul et al. (1999) Neuroscience 88:1-16; Meshul and Allen (2000) Synapse 36:129-142]. In Parkinson's disease, a lesion of either the subthalamic nucleus (STN) or the motor thalamic nucleus relieves the patient of some of the motor difficulties associated with this disorder. In this rodent model, either the STN or motor thalamic nucleus was electrolytically destroyed 2 months following a unilateral 6-OHDA lesions. Following a lesion of either the STN or motor thalamic nucleus in 6-OHDA-treated rats, there was a significant decrease (40-60%) in the number of apomorphine-induced contralateral rotations compared to the 6-OHDA group. There was a significant decrease (<30%) in the basal extracellular level of striatal glutamate in all of the experimental groups compared to the sham group. Following an STN and/or 6-OHDA lesion, the decrease in striatal extracellular levels was inversely associated with an increase in the density of nerve terminal glutamate immunolabeling. There was no change in nerve terminal glutamate immunogold labeling in either the motor thalamic or motor thalamic plus 6-OHDA lesion groups compared to the sham group. The decrease in the number of apomorphine-induced rotations was not due to an increase in TH immunolabeling (i.e., sprouting) within the denervated striatum. This suggests that alterations in striatal glutamate appear not to be directly involved in the STN or motor thalamic lesion-induced reduction in contralateral rotations.

Animals↗
PubMed1998

Topographical organization of opioid peptide precursor gene expression following repeated apomorphine treatment in the 6-hydroxydopamine-lesioned rat.

Many studies have previously described changes in preproenkephalin-A (PPE-A) and preproenkephalin-B (PPE-B) gene expression in the striatum of the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (both with or without dopamine replacement treatment). To date, these studies have either taken the striatum as a whole or have focused on a single subregion of the striatum. However, the striatum is organized into anatomically discrete parallel circuits serving different functions (motor, associative, and limbic). We have therefore employed in situ hybridization to examine the detailed topography of changes in opioid precursor expression following dopamine depletion and subsequent treatment with apomorphine (5 mg/kg twice daily for 10 days). In the untreated 6-OHDA-lesioned striatum PPE-A expression was elevated only in the dorsal (sensorimotor) caudate-putamen. Following apomorphine treatment PPE-A mRNA levels were further raised in the sensorimotor striatum (</=77%) and approximately doubled and tripled in the ventral caudate-putamen (associative) and nucleus accumbens (limbic), respectively. These subsequent elevations were mostly restricted to rostral portions of the striatum. Although unchanged following vehicle treatment, PPE-B gene expression in the lesioned caudate-putamen (sensorimotor and associative) was elevated some 30-fold by apomorphine treatment. A smaller rise (fivefold) was seen in rostral regions of the lesioned nucleus accumbens. Thus, differential regulation of opioid peptide transmission exists in motor, limbic, and associative regions of the striatum and may contribute to the generation of motor and cognitive disturbances following long-term treatment of the dopamine-depleted striatum.

Animals↗
PubMed1993

Growth hormone and gonadotropin secretion in the common carp (Cyprinus carpio L.): in vitro interactions of gonadotropin-releasing hormone, somatostatin, and the dopamine agonist apomorphine.

The effects of salmon gonadotropin-releasing hormone (sGnRH) and the superactive agonist [D-Arg6, Pro9NEt]-sGnRH (sGnRH-A) on growth hormone (GH) and gonadotropin (GtH) release were examined using a perifusion system for pituitary fragments of the common carp (Cyprinus carpio). Perifusion of 2-min pulses of different concentrations of sGnRH or sGnRH-A stimulated a rapid and dose-dependent increase in GH release: ED50 values for sGnRH and sGnRH-A in stimulating GH release were 2.8 +/- 0.7 and 0.5 +/- 0.1 nM, respectively, indicating that the superactivity of sGnRH-A for stimulation of GtH release also applies in induction of GH release. Exposure of the pituitary fragments to 10 nM sGnRH or sGnRH-A alone resulted in increases in GH and GtH release on a similar temporal course. Apomorphine (10, 100, and 1000 nM) significantly inhibited basal and GnRH-induced GtH release in a dose-dependent manner and significantly stimulated basal GH release; however, APO did not enhance GnRH-induced GH release. Somatostatin (100 nM) significantly blocked basal release and 10 nM sGnRH- and sGnRH-A-induced GH release, but was ineffective on GtH release. Treatment with somatostatin (100 nM) in combination with apomorphine (100 nM) caused an increase in sGnRH-induced GH release compared to treatment with somatostatin alone; whereas, on GtH there was a significant decrease in basal and GnRH-induced levels, compared to treatment with somatostatin alone. These results indicate that GH release in common carp is regulated by somatostatin as GH release inhibitor. sGnRH and sGnRH-A act as GH-releasing factors; the mechanisms by which GnRH stimulates GH and GtH secretion are independent. The dopamine agonist apomorphine stimulates GH release and inhibits GtH release directly at the pituitary level.

Animals↗
PubMed1979

Motility and stereotyped behaviour induced by amphetamine and apomorphine on hypophysectomized and on thyroidectomized rats.

The reduction of the hypermotility and stereotyped behaviour induced by amphetamine and apomorphine was used as a criterion for the effectiveness of neuroleptics. Considering the impact of neuroleptics on the hypophysis as well as the relationship between the hypophysis and the thyroid, motility and stereotyped behaviour induced by amphetamine and apomorphine was studied in both hypophysectomized and thyroidectomized rats. In the hypophysectomized rat, amphetamine-induced hypermotility, observed between 1 and 3 hours after administration, was almost 3 times greater than in normal animals. Thyroidectomy resulted in a reversal of the motility effect induced by amphetamine. The stereotyped behaviour induced by apomorphine was practically abolished in both hypophysectomized and thyroidectomized animals.

Amphetamine↗
PubMed2004

Impact of apomorphine on BOLD signal during movement in normals.

Our group investigated modulatory effects of apomorphine on cerebral activation patterns during finger tapping movements in six healthy right-handed volunteers using an established fMRI protocol. Apomorphine application disclosed a reduction of cerebral activation to the contralateral precentral and postcentral gyrus and ipsilateral cerebellum, with a prominent net reduction of BOLD signal in cerebellar areas. These findings contradict those of similar studies performed on dopaminergic function and Parkinson's disease (PD), which predominantly found augmentation of cerebral activation patterns in normal volunteers and PD patients after dopaminergic stimulation. One conceivable explanation for our singular results would be preferred binding of apomorphine to presynaptic dopaminergic receptors, leading to inhibition of endogenous dopamine release and resultant diminished dopaminergic stimulation, reflected in diminished cerebral activation patterns. These findings warrant future consideration and further investigation of possible central inhibitory effects of dopaminergic therapy in functional imaging studies of the dopaminergic system in general and PD in particular.

Adult↗
PubMed1989

Apomorphine-induced alterations in cortical EEG activity of rats. Involvement of D-1 and D-2 dopamine receptors.

EEG activity after activation of dopamine receptors of D-1 and/or D-2 type was studied by using telemetric recordings in rats. Apomorphine, a preferential D-2 agonist, produced a characteristic increase in the power of alpha-1 band (7.00-9.50 Hz) when given in doses mediating stereotypies (0.2 or 0.5 mg/kg s.c.). Low doses produced a general increase in the power of all of the bands except beta-2. In particular, delta activity was enhanced which seems to be in correspondence with the sedation observed after these doses (0.02 and 0.05 mg/kg). Haloperidol in a dose which is assumed to block both D-1 and D-2 receptors (0.1 mg/kg i.p.) completely antagonized the alpha-1 activation produced by apomorphine (0.5 mg/kg). A similar, although not complete inhibition of alpha-1 activation was found after administration of a large dose of the selective D-1 antagonist SCH 23390 (0.2 mg/kg i.p.). The selective agonist at D-2 receptors quinpirole (1.0 mg/kg s.c.) produced a less pronounced activation of the power in the alpha-1 band than apomorphine. In general, there was found to be a good correlation between the activation of the alpha-1 activity and stereotyped behaviour. The results suggest that for the full expression of alpha-1 activation, a pronounced activation of D-2 receptors and at least a minimal activation of D-1 receptors, for instance by the endogenous dopamine, is necessary.

Animals↗
PubMed1988

Apomorphine, d-amphetamine, strychnine and yohimbine do not alter prepulse inhibition of the acoustic startle reflex.

Rats were presented with noise bursts alone or noise bursts 60 ms after presentation of either a 60 dB or an 80 dB prepulse after injection of the dopamine agonists apomorphine (3 mg/kg) or d-amphetamine (4 mg/kg), the glycine antagonist strychnine (1.5 mg/kg) or the alpha 2 antagonist yohimbine (5 mg/kg). Presentation of prepulses inhibited startle, with greater inhibition following an 80 dB versus 60 dB prepulse. Apomorphine, d-amphetamine and strychnine increased overall startle levels but did not attenuate prepulse inhibition, since the absolute change in startle following prepulse presentation was significantly greater after administration of these drugs. A lower dose of apomorphine also increased startle but had no effect on prepulse inhibition using test intervals of 10, 60, 100, 200 or 1000 ms. While these drugs did decrease per cent prepulse inhibition, this seemed wholly attributable to their increasing overall startle levels, rather than a real attenuation of prepulse inhibition. Yohimbine did not alter either startle baseline or prepulse inhibition. The results do not support the conclusion that overactivity of dopamine systems attenuates prepulse inhibition and, in addition, suggest that prepulse inhibition does not result from activation of either glycine or norepinephrine projecting to alpha 2 adrenergic receptors.

Acoustic Stimulation↗
PubMed1988

Apomorphine doses impair the reaction time of fast reacting but not slow reacting rats.

Previously, several studies in our laboratories have linked the ability to initiate movement rapidly (reactive capacity) in several rat strains to markers of nigrostriatal dopamine function. In the present investigation we wished to determine the extent to which fast-reacting (FR) and slow-reacting (SR) rats responded differentially to the effects of dopamine agonist (apomorphine) administration. Fisher 344 rats were operantly conditioned on a shock-avoidance, reactive capacity task which requires extremely fast, ballistic, lever release responses. In FR, but not in SR rats, significant dose-dependent decreases in the per cent of successful avoidance trials were observed in response to apomorphine doses. Moreover, apomorphine brought responding in the FR animals to levels below that of the SR rats. Performance of the SR rats was unaffected by drug treatments. A number of interpretations are consistent with these preliminary data, including the idea that basal differences in speed of reaction and differential responses to a dopamine agonist, antiparkinsonian agent may both be associated with a similar mechanism: differential activation of compartmentalized striatal efferent systems.

Animals↗
PubMed1987

Apomorphine-induced yawning in rats is abolished by bilateral 6-hydroxydopamine lesions of the substantia nigra.

Apomorphine-induced yawning was studied in male rats with bilateral 6-hydroxydopamine lesions of the substantia nigra. Apomorphine 10, 20 and 50 micrograms/kg SC induced dose-dependent yawning in unoperated controls and animals with sham lesions. In the lesioned animals (in which the mean striatal dopamine depletion was 67%), the maximum yawning response rate was greatly attenuated with no evidence that the dose response curve was shifted in either direction. Furthermore, blockade of yawning in the lesioned animals was not simply due to suppression by other stereotyped behaviours, since there was no evidence of increased sniffing or chewing in these animals. These data provide further support for the hypothesis that apomorphine-induced yawning is mediated by dopamine autoreceptors and requires intact nigrostriatal projections.

Animals↗
PubMed1987

Anti-apomorphine effects of phenothiazine drug metabolites.

The potencies in producing muscle relaxation, and in antagonizing apomorphine-induced climbing and hypothermia in mice, were examined for chlorpromazine, levomepromazine and their main metabolites, and for fluphenazine and 7-hydroxy fluphenazine. 3-Hydroxy chlorpromazine was more potent than chlorpromazine in antagonizing apomorphine-induced climbing, while levomepromazine and 3-hydroxy levomepromazine were equipotent in this test. The 3-hydroxy metabolites of chlorpromazine and levomepromazine were more potent than the parent compounds in antagonizing hypothermia, and had significantly weaker muscle relaxant effects than the parent compounds. The 7-hydroxy and N-monodesmethyl metabolites were generally less potent that the parent compounds in antagonizing apomorphine-induced effects. N-Monodesmethyl levomepromazine had a pronounced muscle relaxant effect, like levomepromazine itself. The sulphoxide metabolites of chlorpromazine and levomepromazine were inactive in all tests. Their potencies in these tests indicate that among the metabolites 7-hydroxy chlorpromazine, N-monodesmethyl chlorpromazine and 3-hydroxy levomepromazine, which have all been identified in plasma from patients, may contribute to the antipsychotic effects of the drugs, and furthermore that N-monodesmethyl levomepromazine may contribute to the sedative effects of levomepromazine.

Animals↗
PubMed1996

Circling behaviour induced by apomorphine after lesions of the habenula.

Apomorphine, 2 mg/kg (s.c.) produced significant contralateral turning in rats with unilateral radiofrequency lesions of the habenula nucleus over a test period of 60 min when tested at post-surgery days 3, 7, and 14. Levels of contralateral circling were not significantly increased when the animals were tested on days 21 and 28, although a contralateral bias was still observed. Rotation induced by apomorphine was completely blocked by the administration of haloperidol (0.3 mg/kg i.p.), and there was no behavioural asymmetry in lesioned animals following administration of saline or a high dose of haloperidol (2 mg/kg i.p.). These results indicate that unilateral habenula lesions lead to imbalance of dopaminergic activity, which is expressed as contralateral circling when the animal is challenged with apomorphine.

Animals↗
PubMed1986

The effects of apomorphine, d-amphetamine and chlorpromazine on the aggressiveness of isolated Aequidens pulcher (Teleostei, Cichlidae).

Apomorphine, d-amphetamine, chlorpromazine and dopamine, added to the aquarium water, were tested for their effects on the aggressive responses of isolated fish to mirrors and to models, compared with the responses of the same fish as non-treated controls tested at the start of, in the middle, and at the end of the experiment (Experiment 1). The effects of d-amphetamine administered by intracranial injection were also evaluated for responses to mirror presentations (Experiment 2). The three sets of controls in Experiment 1 indicate that the responses of the fish apparently changed over the 32-day experiment: they became more aggressive to mirrors whilst reacting less to models. Dopamine had no behavioural effect. Immersion in either apomorphine or d-amphetamine resulted in increased swimming activity, accompanied by apparent behavioural stereotypy. Immersion in apomorphine (Experiment 1) and intracranial injections of d-amphetamine (Experiment 2) also resulted in reduced aggression. Likewise, chlorpromazine also reduced some measures of overt aggression, whilst the appearance of other behaviours suggested that there is also an increased tendency to withdraw from the stimulus. It is concluded that the dopaminergic system plays an important role in the regulation of aggressive behaviour in this cichlid fish.

Aggression↗
PubMed1976

[Amantadine: aggressive effect; effect on apomorphine-induced aggressivity in the rat].

In rats characterized by aggressive behaviour induced by apomorphine, only amantadine in doses of 10 mg/kg i.v. and 50 mg/kg i.p. induces a very slight aggressive effect, but in doses of 30 and 50 mg/kg i.p. it inhibits the aggressive behaviour induced by 1 mg/kg apomorphine. The effect is dose-related and it is more pronounced when amantadine (50 mg/kg i.p.) is injected 30 min rather than 1 h before apomorphine.

Aggression↗
PubMed1976

Influence of pheniramine and chlorpheniramine on apomorphine induced compulsive gnawing in mice.

In mice, apomorphine (10 mg/kg s.c.) does not induce a compulsion to gnaw, but pretreatment with antihistamines, viz. pheniramine, chlorpheniramine and mepyramine, in doses ranging from 30 to 60 mg/kg i.p. caused gnawing activity. Mepyramine showed significantly less effect when compared to the other two agents. Antihistamines are known to influence the activity of biogenic amines in central nervous system. The potentiation of apomorphine-induced gnawing by antihistamines might depend upon the reciprocal balance between dopaminergic and cholinergic systems. This was tested by blocking biosynthesis of biogenic amines or by blocking their receptors. The potentiation of gnawing was antagonised by physostigmine (0.25 mg/kg) or blocked by pretreatment with alpha-methyl-p-tyrosine (alpha-MPT) (4 X 150 mg/kg) and bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulphide (FLA) (40 mg/kg), while p-chlorophenyl alanine (p-CPA) (3 X 100 mg/kg) had no effect. Similarly, phenoxybenzamine (30 mg/kg) and haloperidol (1.0 mg/kg) inhibited gnawing activity, but methysergide (10 mg/kg) had no effect. Furthermore, pretreatment with tetrabenazine (20 mg/kg) and L-Dopa (200 mg/kg) did not affect gnawing activity. It is concluded that both pheniramine and chlorpheniramine potentiate apomorphine gnawing by upsetting the cholinergic and dopaminergic balance in favour of dopaminergic dominance.

Animals↗
PubMed1984

Methylphenidate, apomorphine, THIP, and diazepam in monkeys: dopamine-GABA behavior related to psychoses and tardive dyskinesia.

In eight monkeys (Cercopithecus aethiops), previously treated with haloperidol for 4-14 months, we have examined the behavioral effect of: (1) methylphenidate vs apomorphine; (2) 4,5,6,7-tetrahydroisoxazolo-(5,4-c)-pyridin-3-ol(THIP, a GABA agonist) vs diazepam; and (3) THIP and diazepam in methylphenidate-induced behavior. Methylphenidate (0.5-5.0 mg/kg) and apomorphine (0.1-0.5 mg/kg) both increased locomotion, but otherwise exhibited different behavioral profiles. Methylphenidate induced repetitive movements of head, limbs, and trunk, and hallucinatory-like behavior, but not oral hyperkinesia (licking and gnawing), whereas apomorphine preferentially caused oral hyperkinesia. THIP produced a syndrome of bradykinesia, dystonia, ataxia, myoclonus, sedation, and decreased responsiveness, whereas diazepam produced only bradykinesia, ataxia, sedation, and decreased responsiveness, but not dystonia and myoclonus. Methylphenidate-induced locomotion and repetitive movements were reduced by THIP and diazepam, whereas hallucinatory-like behavior was markedly aggravated by THIP, but not by diazepam.

Animals↗
PubMed1977

Effect of apomorphine on the antinociceptive activity of morphine.

Apomorphine pretreatment potentiated the analgesic effect of morphine in a dose-dependent manner both in rats and in mice measured by five different tests (writhing, hot plate, inflamed foot, tail-pinch and tail-flick procedures). Furthermore, apomorphine augmented the antinociceptive activity of morphine in tolerant animals as well. In morphine dependent mice the nalorphine precipitated jumping--a withdrawal symptom--was found inhibited by apomorphine treatment. The results are discussed in the light of the numerous but contradictory data available in the literature.

Analgesics, Opioid↗
PubMed1979

Impairment by apomorphine of one-trial passive avoidance learning in mice: the opposing roles of the dopamine and noradrenaline systems.

Pretraining administration of the dopaminergic stimulant apomorphine (0.25--16 mg/kg) impaired retention performance of mice on a one-trial passive avoidance task. Only with a very high dose (16 mg/kg) of this drug did the effect seem related to an interference with memory formation processes. Of the dopamine receptor-blocking agents used, haloperidol (0.125--1 mg/kg), but not chlorpromazine or clozapine (0.25--4 mg/kg), prevented the apomorphine effect. Phenoxybenzamine (8 mg/kg), a noradrenaline receptor-blocker, antagonized the haloperidol effect and, when combined with a subeffective dose of apomorphine, impaired passive avoidance learning. The results obtained are interpreted in terms of the proposed inhibitory actions exerted by central noradrenaline on dopamine systems of the brain.

Animals↗
PubMed1985

Effect of diazepam, apomorphine and haloperidol on the audiogenic immobility reaction and on the open field behavior.

Weanling rats were treated with diazepam, apomorphine, and haloperidol to study the influence of the dopamine (DA) system on the audiogenic immobility reaction and open field locomotory behavior. Treatment with diazepam (0.025, 0.05, and 0.1 mg/kg) caused a dose-dependent shortening of the duration of the immobility response. Treatment with apomorphine (0.125, 0.25, and 0.50 mg/kg) shortened both the immobility reaction and the latency to leave the spot where the animal was first placed in the open field (latency for first crossing). Locomotor activity increased in a dose-dependent fashion. Both grooming and rearing showed biphasic dose response curves, with a maximum occurring at the 0.125 mg/dose for grooming and at the 0.25 mg/dose for rearing. Haloperidol (0.06 mg/kg) exerted opposite effects to those of apomorphine, but also produced increased running during the auditory stimulation (flight distance). Using the immobility reaction as an expression of fear, we concluded that activation of the DA system decreases while inhibition of the DA system increases fear. It was hypothesized that the DA system exerts an inhibitory function in the expression of fear.

Acoustic Stimulation↗