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Results for “Apomorphine”

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At least 19 recordsLinked to original sources
PubMed1976

Time-course of apomorphine in the brain of the immature rat after apomorphine injection.

The time-course of apomorphine in brain was studied in 7-day-old and young adult rats following i.p. injection of 10 mg/kg apomorphine. In the adult animals continuous stereotypes behaviour (SB) commenced within 1-2 min and was no longer present at 75 min. The peak concentration of apomorphine was present at 5 min and then declined exponentially (half-life = 10.5 min); only trace amounts (less than 0.01 mug/g) were present at 90 min. In the immature rat apomorphine induced an initial phase of intermittent locomotion lasting about 10 min after which the rats appeared sedated; 60-80 min after injection intermittent SB emerged and terminated 150-180 min after the apomorphine injection. The peak brain concentration of apomorphine was present at 10 min and then declined exponentially (half-life = 28 min). Significant amounts of apomorphine were still present in brain at 150 min and trace amounts evident at 180 min. The reason for the delayed onset of SB in the immature rat is unclear. The longer half-life is presumably related to incomplete development of enzyme systems metabolizing apomorphine in the immature animal.

Animals↗
PubMed1978

Effects of apomorphine and apomorphine-L-dopa-carbidopa on alcohol post-intoxication symptoms.

In a randomised double-blind clinical trial on 58 gamma-alcoholics, the effect of apomorphine given orally in individual subemetic doses was compared with apomorphine-L-dopa-carbidopa and with placebo. No positive effects of treatment with apomorphine, or with the combination apomorphine-L-dopa-carbidopa, on alcohol consumption or post-intoxication symptoms could be demonstrated. In the group which received the combination apomorphine-L-dopa-carbidopa, the post-intoxication symptoms lasted significantly longer than in the other two groups.

Adult↗
PubMed1978

Apomorphine stereotypies and transmitter mechanisms in the striatum. I. Changes in the apomorphine stereotypies caused by drugs acting on the GABA-ergic, dopaminergic and cholinergic transmission.

Experiments on male albino mice were carried out in order to determine the effects of drugs connecting with the GABA-ergic, dopaminergic and cholinergic transmission, on apomorphine stereotypies. The agents acting on GABA-ergic transmission are found to reduce the intensity of apomorphine stereotypies in the following order (arranged from strongest to weakest effect and expressed in doses of microgram per mouse: GABA (100), aminooxyacetic acid (5), diazepam (20), picrotoxin (1), GABA (10), semicarbazide (30), picrotoxin (0.1). The agents acting on the dopaminergic transmission also reduce apomorphine stereotypies in the following order: haloperidol (20;2), L-DOPA (500 mg/kg, i. p.), alpha-methylparatyrosine (150 mg/kg, i. p.) diethyldithiocarbamate (200). The strongest antagonistic effect in the two groups of agents studied was found for haloperidol. The agents acting on the cholinergic transmission (agonists and antagonists of muscarinic and nicotinic cholinoreceptors) have no significant effect on apomorphine stereotypies. It is assumed that the striatum is not the only brain structure responsible for apomorphine stereotypies.

Aminooxyacetic Acid↗
PubMed1977

Subcutaneous injections of apomorphine, stimulus generalization and conditioning: serious pitfalls for the examiner using apomorphine as a tool.

This report shows that stimulus generalization occurs in rats conditioned by a single injection of apomorphine. The data suggest that apomorphine initially acts as an unconditioned stimulus (UCS) of an unconditioned response (UCR) that, in turn, produces stimuli which become conditioned stimuli (CS) of a conditioned response (CR) having a nature identical to that of the UCR. The study also shows that behaviour elicited by a subcutaneous injection of apomorphine depends on the part of the body selected for administration. The mentioned properties should be taken into account when apomorphine is used as a tool in studies on brain and behaviour.

Animals↗
PubMed1977

[Effects of hypothalamus and globus pallidus lesions and of apomorphine injections into the globus pallidus, caudate nucleus, substantia nigra and septum on the aggressive behavior induced by apomorphine treatment of rats (author's transl)].

Intraspecific apomorphine-induced aggressive behavior in the rat was not affected following electrolytic lesions of the ventromedial hypothalamus. Some inhibition of the aggressive behavior was found after lateral lesions and an almost total suppression after destruction of globus pallidus. These results, as well as those following localized injections of apomorphine into the septum, substantia nigra, caudate nucleus, and globus pallidus suggested that the latter anatomical region may be the major site of the action of apomorphine in the behavior studies. The role of acetylcholine is discussed.

Aggression↗
PubMed1976

[Aggressive behaviour induced by apomorphine: relations with some elements of the behavioural profile and with the sensitivity to apomorphine (author's transl)].

Aggressive rats could be differentiated from non-aggressive rats on a lower rate of rearing reactions in the open-field activity, as well as on a weaker aptitude for learning, increasing with the complication of the test. The two groups of rats had comparable activity, and a comparable response to pain. Apomorphine decreased the number of rearing reactions and defecations on open-field activity in the same manner in non-aggressive rats as in aggressive animals. In the usual housing conditions, apomorphine increased similarly locomotor activity in both groups, but in observation cages of "emotional" type, the increase was much more pronounced in aggressive rats than in non-aggressive animals.

Aggression↗
PubMed1991

Effects of selective D1 and D2 dopamine antagonists on the development of behavioral sensitization to apomorphine.

The objective of the present study was to determine whether the development of behavioral sensitization to apomorphine could be blocked by either D1 or D2 selective dopamine antagonists. In three experiments, male rats received 10-21 daily injections of a selective D1 (SCH 23390; 0 or 0.5 mg/kg IP) or D2 (sulpiride; 0, 30, or 100 mg/kg IP) antagonist followed by an apomorphine (0 or 1.0 mg/kg SC) injection. In two experiments, the rats were tested for locomotor activity in photocell arenas after the daily injections. In all experiments, the rats were tested for sensitization to apomorphine following the training phase. The results indicated that apomorphine produced a progressively greater increase in locomotor activity with each injection, and this apomorphine-induced increase in activity was completely blocked by both sulpiride and SCH 23390 treatments. However, although both sulpiride and SCH 23390 blocked apomorphine-induced activity, only SCH 23390 injections prevented the development of sensitization to apomorphine. That is, rats pretreated with sulpiride and apomorphine displayed significant sensitization when subsequently tested with a challenge dose of apomorphine alone. These findings suggest that the development of behavioral sensitization to apomorphine is related specifically to the stimulation of dopamine D1 receptors.

Analysis of Variance↗
PubMed1977

Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei.

Changes in stereotyped sniffing, biting and hyperactivity induced by apomorphine and D-amphetamine in the rat were determined after bilateral 6-hydroxy-dopamine (6-OHDA) lesions (8-16 micron/4micron6) of the extrapyramidal caudate-putamen (CP) (anterior and centre), globus pallidus (GP) and substantia nigra (SN), the mesolimbic nucleus (ACB), tuberculum olfactorium (TUO) and central amygdaloid nucleus (ACE). Lesions were also induced in the medial forebrain bundle in the lateral hypothalamus (LH). The 6-OHDA lesions of the CP reduced amphetamine biting but not sniffing or hyperactivity. Centrally placed 6-OHDA failed to modify any response to apomorphine but anterior locations reduced apomorphine biting. Both lesion locations led to a 45-65% reduction in striatal dopamine (DA) content, but the anterior location also involved depletions of mesolimbic DA. 6-OHDA lesions of the GP reduced striatal DA by 62% but initially potentiated before reducing both apomorphine and amphetamine biting. These lesions also potentiated amphetamine hyperactivity but other parameters were unmodified. The LH and SN lesions reduced striatal and mesolimbic DA by 75-80% and potentiated apomorphine biting. The LH lesions reduced amphetamine biting and hyperactivity but the SN lesions initially potentiated these responses. 6-OHDA lesions of the ACB reduced the DA content of this nucleus by 72% but had little effect on the TUO: these lesions reduced the duration of amphetamine hyperactivity and potentiated apomorphine biting. In contrast, equally selective lesions of the TUO (80% DA depletion) enhanced the locomotor activity response to both apomorphine and amphetamine; apomorphine biting was also increased but other parameters were unmodified. Lesions of the ACE depleted amygdaloid DA by at least 80% and reduced or abolished apomorphine and amphetamine biting in the chronic stage. The results indicate that the sites for mediation of sterotyped sniffing, biting or hyperactivity are not the same for apomorphine and amphetamine, and that each behavioural state involves the functioning of more than one DA-containing area.

Amygdala↗
PubMedDate not supplied

Penfluridol blockade of apomorphine: dependence of duration on species and endpoint.

Penfluridol, at relatively low doses, blocks apomorphine-elicited emesis in dogs and apomorphine-elicited floor pecking in pigeons for over a month. In mice tested for apomorphine-elicited hypothermia, and in rats tested for apomorphine-elicited chewing behavior, however, the anti-apomorphine activity of penfluridol does not persist for longer than 2-3 days even when high doses of penfluridol are given. In rabbits tested for apomorphine-induced hyperthermia and gnawing, on the other hand, penfluridol blocks apomorphine for about a week. Thus, of the 5 species tested, only in rabbits does the duration of penfluridol's anti-apomorphine action approximate the 1-week duration reported from human therapeutic trials. In mice given high-dose penfluridol apomorphine consistently elevates body temperatures, rather than exerts its usual hypothermic response. Conversely, in rabbits given penfluridol apomorphine tends slightly to decrease body temperatures, rather than exert its usual hyperthermic response.

Animals↗
PubMed1991

Apparent enhancement by SCH 23390 of apomorphine-induced locomotor activity in mice.

Effects of the dopamine (DA) D1 antagonist SCH 23390 and the DA D2 antagonist (-)-sulpiride on apomorphine-induced characteristic changes in spontaneous motor activity were investigated in mice using the system we have devised for automatically analyzing animal behaviors in mice. Apomorphine (3 mg/kg, SC) markedly increased parameters of spontaneous motor activity such as locomotor activity and rearing time. Apomorphine-induced increase in locomotor activity had peaks at 5-20 and 30-50 min after administration, and its trough was closely related to the marked increase in rearing time induced by this agonist. Apomorphine-induced locomotor activity accumulated over a 40-min period from 5 to 45 min after apomorphine injection, during which apomorphine-induced increase in rearing time peaked, was significantly increased by intraperitoneal administration of 0.03 and 0.1 but not 0.01 mg/kg SCH 23390. Apomorphine-induced increase in rearing time was dose-dependently depressed by this antagonist. In contrast, (-)-sulpiride (10-40 mg/kg, IP) decreased apomorphine-induced increases in rearing time and locomotor activity rather than enhancing the latter parameter. These data suggest that the apparent enhancement by SCH 23390 of apomorphine-induced locomotor activity is mediated through DA D1 receptors and does not always correlate with depression of apomorphine-induced rearing behavior in mice.

Animals↗
PubMed1992

Inhibition of nigral dopamine neurons by systemic and local apomorphine: possible contribution of dendritic autoreceptors.

Peripheral administration of low doses of dopamine agonist apomorphine induces a strong and short-latency inhibition of dopamine neurons in the substantia nigra, presumably via the activation of somatodendritic autoreceptors. We studied the site of action of apomorphine in anesthetized rats using volume-controlled pressure microejection combined with single unit recordings. Microapplication of apomorphine in the immediate vicinity of nigral dopamine neurons did not mimic the effect of intravenous administration of apomorphine (50 micrograms/kg), regardless of the concentration or volume used (10(-10)-10(-2) M, 10-100 nl). In contrast, the inhibition produced by systemic apomorphine was mimicked by drug application at a site 300 microns lateral and 600 microns ventral from the recording site in the zona reticulata of the substantia nigra, a region rich in dendrites of dopamine neurons. The inhibition induced by such a distant application of apomorphine could be reversed by systemic injection of D2, but not D1, receptor antagonists. Non-dopaminergic substances such as GABA, bicuculline or lidocaine were more effective when ejected close to rather than distant from the recording site, in a manner opposite to that of apomorphine. Similar to apomorphine, dopamine and D2 receptor agonists were more potent when intranigral applications were made at sites distant from, rather than close to, the recorded dopamine cells. Ejection of D2 antagonists in the substantia nigra zona reticulata attenuated the inhibitory effect of subsequent systemic apomorphine. Our results, together with other previous studies on the location of D2 receptors on dopamine neurons, suggest that peripheral administration of low doses of apomorphine inhibits nigral dopamine neurons by acting at D2 receptors located on the dendrites of these neurons.

Animals↗
PubMed1991

Selective effects of low doses of apomorphine on spatiotemporal contrast sensitivity in healthy volunteers: a double-blind placebo-controlled study.

1. Apomorphine (1 and 5 micrograms kg-1) and placebo were given to nine normal volunteers, using a Latin-square design and double-blind procedures. The visual perception of static and moving patterns (static and motion contrast sensitivity) was evaluated before and 15 min after the dose administration. 2. Apomorphine (1 and 5 micrograms kg-1), as compared with placebo, led to a significant overall reduction of the visual perception of movement. This effect was dose-related, and apomorphine (5 micrograms kg-1) induced a more pronounced decrease in the visual perception of movement than apomorphine (1 microgram kg-1). With apomorphine (5 micrograms kg-1), the reduction was more pronounced for low spatial frequencies, and was linearly inversely correlated to the spatial frequency for a temporal frequency of 3 Hz. Finally, no significant effect of apomorphine was observed for sensitivity to static patterns. 3. Several non exclusive hypotheses may be suggested: The effects of apomorphine may result from stimulation of retinal D1- and/or D2-dopaminergic receptors. Apomorphine may increase the surround inhibition of ganglion cells' receptive-fields. This modification of the centre-surround balance may explain the decrease in contrast sensitivity for low spatial frequencies. The specific effects of apomorphine on the visual perception of movement support the hypothesis that apomorphine preferentially affects the magnocellular pathway which mediates sensitivity to moving patterns.

Adult↗
PubMed1991

Effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine inhibition of sensorimotor gating of the startle response in the rat.

Previous work suggests that the dopamine agonist apomorphine decreases prepulse inhibition (PPI) of the acoustic startle response in rats. To better understand the dopamine substrates of this apomorphine response, we investigated the effects of four pharmacologically distinct dopamine antagonists on the apomorphine-induced loss of PPI. Apomorphine (0.5 mg/kg s.c.) markedly decreased PPI for all prepulse intervals tested. This effect of apomorphine on PPI was reversed by pretreatments with the D2 antagonists spiperone and raclopride but not by pretreatment with the D1 antagonist SCH 23390. The atypical antipsychotic clozapine exhibited an "inverted-U" shaped dose-response curve, reversing the apomorphine-induced loss of PPI at low doses but not at high doses. High doses of both SCH 23390 and clozapine decreased PPI independent of apomorphine treatment. The effects of apomorphine on baseline startle amplitude were also differentially modified by these drugs: apomorphine potentiated startle amplitude in spiperone- and raclopride-pretreated animals, but apomorphine decreased startle amplitude in animals pretreated with SCH 23390 or high doses of clozapine. Prepulse inhibition has been shown to be markedly impaired in humans with schizophrenia. Since our present findings suggest that the activation of D2 dopamine receptors is responsible for the loss of PPI in rats, overactivity of D2 dopamine receptors might also be a substrate for PPI deficits in schizophrenia.

Analysis of Variance↗
PubMed1991

Absorption of apomorphine by various routes in parkinsonism.

We wanted to determine the absorption and clinical effect of sublingual (SL) and transdermal apomorphine in parkinsonism. Patients received single SL apomorphine doses (N = 7) and the absorption was compared with parenteral (N = 5) and oral (N = 4) doses. One patient received a transdermal dose of apomorphine. The relative bioavailability of SL apomorphine ranged from 10 to 22% of a parenteral apomorphine dose. Oral apomorphine was less than 4% bioavailable, and the transdermal dose did not produce detectable plasma levels. Three patients with motor fluctuations responded to SL apomorphine, with a latency to effect of 20-40 min and a duration of effect of 15-100 min. One patient used SL apomorphine as an adjunct with levodopa, and during 1 month reported a large decrease in "off" periods. We conclude that apomorphine is effectively absorbed by the sublingual route.

Absorption↗
PubMed1975

Apomorphine pecking in the pigeon.

Pecking activity elicited by apomorphine was studied quantitatively in intact and thalamic pigeons. While apomorphine pecking is easily observed in the intact pigeon, it is absent in the acute thalamic animal. I reappears, however, in the chronic preparation simultaneously with the recovery of spontaneous pecking. Apomorphine pecking is described by satiation and increased by fasting. Reticular stimulation produces reversible blockade of both apomorphine and spontaneous pecking with the same parameters, without increase in heart rate. Apomorphine pecking can be observed only in the presence of visual contrast, and is always aimed at the contrast points or edges. A decrease in contrast produces a decrease in the number of pecks delivered to the contrast points and an increase in those missing the target, while the total number of pecks delivered in a unit time is unaffected. A lowering of the background luminance is followed by a decrease in the total number of pecks, which is mostly due to a reduction of those aimed at the contrast points. All these findings are discussed and it is concluded that: i) apomorphine exerts an excitatory action (direct or indirect) on the hypothalamic feeding centers; hence apomorphine pecking can be considered as a pharmacologically motivated behavior; ii) visual contrast exerts a dual action on apomorphine pecking, namely it acts both as triggering stimulus and goal object; iii) the decrease in apomorphine pecking induced by lowering the ambient light intensity is probably due to a decrease in the level of the general arousal.

Animals↗