Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Apomorphine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1992

Behavioral effects of amphetamine and apomorphine after striatal lesions in the rat.

It is well established that denervation of the dorsal striatum by its dopaminergic afferents attenuates the stereotyped response to d-amphetamine, which can be considered as an extreme form of motor activation. However, it is difficult to sustain the view that this structure serves primary motor control function because the role of dopamine in the striatum remains difficult to understand. In this study, we compared the effects of two dopaminergic agonists, d-amphetamine and apomorphine, after dorsal striatal lesions with ibotenic acid using a computerized scoring of the behavior. Although d-amphetamine- and apomorphine-induced locomotor activity was no different between lesioned and nonlesioned rats in photobeam activity cages, the structure of their behavioral pattern was quite different. Freezing, a usual response after d-amphetamine, was blocked by the lesion. Lesioned rats exhibited less standing than nonlesioned after d-amphetamine, apomorphine, or saline treatment. Moving was increased in lesioned rats after a low dose of d-amphetamine (0.5 mg/kg) or apomorphine (0.5 mg/kg), while d-amphetamine induced in the same rats an increase of rearing. Stereotyped behavior after both drugs at high doses was not affected by striatal lesion. These results indicate that the dorsal striatum is not involved only in the control of stereotypy, as has been suggested using 6-hydroxydopamine lesions, but also plays a major role in the mediation of behavioral activation in response to stimulant drugs.

Animals↗
PubMed1992

Hippocampal oxytocin mediates apomorphine-induced penile erection and yawning.

Repeated episodes of penile erection and yawning can be induced in male rats either by low doses of the dopaminergic agonist apomorphine or by oxytocin given systematically or into a lateral ventricle (ICV), respectively, or after microinjection of the two substances directly in the paraventricular nucleus (PVN) of the hypothalamus. These behavioral responses are prevented in a dose-dependent manner by the ICV administration of the potent oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin. In contrast, the PVN injection of d(CH2)5Tyr(Me)-Orn8-vasotocin (1-30 ng), while effective in preventing oxytocin effect, was unable to prevent apomorphine response. On the other hand, apomorphine-, but not oxytocin-induced penile erection and yawning was prevented by electrolytic lesion of the medial septum (MS). Such a lesion decreased oxytocin content by about 45% in the hippocampus. The above results suggest that the hypothalamic-hippocampal oxytocinergic pathway mediates apomorphine-induced penile erection and yawning and that oxytocin is involved at different levels in the CNS for the control of these behavioral responses.

Animals↗
PubMed1993

Influence of beta-casomorphins on apomorphine-induced hyperlocomotion.

Derivatives of beta-casomorphin Tyr-Pro-Phe-Pro-Gly and their des-Tyr1-derivatives were investigated on the model of apomorphine-induced hyperlocomotion (1 mg/kg = 3 microM/kg, IP). D-Pip4 CM 5 (5 nM) inhibited the apomorphine hypermotility completely, while D-Phe3 CM 5 (5 nM) and D-Pro4 CM 5 (5 nM) decreased it only to about 50%. The normal exploration was nearly completely inhibited by D-Pro4 CM 5 (40 nM), by D-Pip4 CM 5 (5 nM) depressed to 20%, and by D-Phe3 CM 5 (10 nM) to 35%. The maximum inhibition of apomorphine-induced hyperlocomotion by the des-Tyr-casomorphin derivatives was about 50%. The dose-response curves were U-shaped. The exploratory activity was not significantly influenced. The mode of action and the involvement of different neurotransmitter systems in the inhibitory effect of beta-casomorphin derivatives on apomorphine hyperlocomotion are discussed.

Amino Acid Sequence↗
PubMed1993

Apomorphine sensitization effects: evidence for environmentally contingent behavioral reorganization processes.

Apomorphine-induced behavioral sensitization was investigated with a Pavlovian conditioning paradigm. Rats were administered apomorphine (2.0 mg/kg SC) daily for 7 days either paired or unpaired with a 10-min test environment placement. Initially, apomorphine induced hypolocomotion, but by treatment day 5, hyperlocomotion developed. Utilizing a videoimage analysis program which quantitated angular movement, it was determined that the increase in locomotion induced by repeated apomorphine treatment was due to an increase in rotational locomotion. Critically, rotation per se did not increase, but rather wide angle rotation toward the periphery of the test environment increased. Furthermore, a directional bias of rotation developed and stabilized which was unrelated to the animal's initial asymmetry bias. This emergence of a new locomotion pattern in conjunction with hyperlocomotion pointed to the need to reconceptualize behavioral sensitization phenomena into a new framework consistent with a progressive change in behavioral structure. Behavioral reorganization is presented as an alternative formulation to that of behavioral sensitization, as a drug-environment interactive process which is more compatible with the behavioral dynamics that emerge with repeated intermittent dopaminergic psychostimulant drug treatment.

Animals↗
PubMedDate not supplied

Apomorphine affects cholecystokinin content via preferentially D1 or D2 dopamine receptor according to the regions of the rat brain.

Cholecystokinin octapeptide-like immunoreactivity (CCK-8IR) was measured in several regions of the rat brain after the intraperitoneal administration of apomorphine, SKF-38393 (D1 agonist), LY-171555 (D2 agonist). In the medial prefrontal cortex and striatum, apomorphine and SKF 3839 decreased CCK-8IR. In the anterior and posterior nucleus accumbens, on the other hand, the inhibitory effect of apomorphine was mimicked by LY-171555. These results suggest that apomorphine affects CCK-8IR via either the D1 dopamine (DA)-receptor or D2 DA-receptor according to the brain region.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Methamphetamine- and apomorphine-induced changes in spontaneous motor activity using a new system to detect and analyze motor activity in mice.

A new system was devised to detect animal spontaneous motor activity in more detail, and methamphetamine- and apomorphine-induced changes in spontaneous motor activity were analyzed using this system. The system consists of a doughnut-shaped cage with 36 units of detectors. Scanning of each detector unit was three-dimensionally carried out, and then scanning data were fed into a personal computer. These steps were completed within 0.1 sec and repeated. Spontaneous motor activity was analyzed as changes in parameters, such as total activity, locomotor activity, vertical activity (the number of rearings and the rearing time), motion time, and average speed. Regarding dependence on the dosages of methamphetamine and apomorphine, the time courses of changes in total activity and locomotor activity markedly differed from those for changes in vertical activity. Changes in the numbers of rearings and rearing time induced by 2 mg/kg methamphetamine peaked 40-80 min after administration, whereas those in other parameters did so 15-25 min after. Three mg/kg apomorphine-induced changes in total activity and locomotor activity showed two peaks 10-15 and 40-50 min after administration, respectively. At the same dosage, apomorphine markedly increased rearing time with slight but not significant effects on the number of rearings. These effects peaked 20-30 min after administration. These results indicate this system to be quite useful to detect and analyze drug-induced changes in spontaneous motor activity.

Animals↗
PubMed1993

Delayed effects of neonatal hippocampal damage on haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors in the rat.

The developmental effects of neonatal excitotoxic ventral hippocampal (VH) damage on behaviors related to dopaminergic (DA) transmission in the basal ganglia were investigated in the rat. Ibotenic acid (in Lesion) or artificial cerebrospinal fluid (in Sham) was infused into the VH of 7-day-old (PD7) rat pups. Haloperidol-induced (1 mg/kg, i.p.) catalepsy and apomorphine-induced (0.75 mg/kg, s.c.) stereotypic behaviors as well as locomotion were assessed in Sham and Lesion rats prior to (PD35) and after puberty (PD56). On PD35, Lesion and Sham animals did not differ in induced catalepsy or stereotypy. On PD56, however, Lesion animals were less cataleptic following haloperidol injection and manifested supersensitivity to apomorphine as compared to Sham rats. At both, PD35 and PD56, locomotor activity after apomorphine was significantly increased in Lesion animals as compared with controls. These results indicate that the neonatal excitotoxic VH lesion results in a unique time-dependent pattern of behavioral changes related to striatal DA transmission. Moreover, the response to apomorphine differs qualitatively from that previously reported after the analogous lesion induced in adult animals in which stereotypy was reduced. These findings suggest that early hippocampal deafferentation affects the development of other brain regions, such as the medial prefrontal cortex, that are also involved in the regulation of striatal DA function.

Animals↗
PubMed1986

Apomorphine reverses direction of asymmetry in facial scanning after 10 days of unilateral vibrissae removal in rat: vibrissotomy-induced denervation supersensitivity?

Sensorimotor asymmetries of hemivibrissotomized rats were investigated in an open field. To examine possible behavioral plasticity after unilateral removal of the vibrissae, we compared two groups of rats which had experienced the sensory imbalance for different durations. One group was shaved on one side of the face daily for 10 days before behavioral testing (group 10-Days). The other group was first shaved 4 h prior to the behavioral testing and was sham-shaved for the preceding 10 days (group 4-H). On day 11, the undrugged behavior was examined, and then, one hour later, the behavior induced by apomorphine (0.75 mg/kg, s.c.) was analyzed. In the undrugged state both groups tended to scan the walls of the enclosure with the vibrissae side of the face. After injection of apomorphine, the 4-H group also scanned the walls preferentially with the vibrissae side. In contrast, the 10-Days group reversed the scanning asymmetry under the influence of this drug. That is, animals in this latter group now preferred to scan the walls with the shaved side of the face. These findings are suggestive of a plasticity in dopamine transmission subsequent to unilateral removal of vibrissae. The reversal in direction of asymmetry under apomorphine of the 10-Days group is reminiscent of the apomorphine-induced reversal in sensorimotor asymmetries found after unilateral 6-hydroxydopamine lesion of the substantia nigra, which has been attributed to dopamine receptor supersensitivity.

Animals↗
PubMed1990

Relation between motor asymmetry and direction of rotational behaviour under amphetamine and apomorphine in rats with unilateral degeneration of the nigrostriatal dopamine system.

The study examines whether in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra, the direction of amphetamine- and apomorphine-induced rotations is determined by a bias to step more frequently with one hindleg. Results show that there is a strong asymmetry in usage of hindlegs under apomorphine but a weak one under amphetamine. Moreover, under apomorphine, virtually all steps are backward. Under amphetamine, however, steps are directed both backward and forward, although backward steps are relatively more prevalent when striatal dopamine depletion is nearly total. The different styles of rotation reflect the activation of pure turning under apomorphine, and turning combined with forward progression under amphetamine. It is suggested that presence of forward progression during turning depends on the capacity to modulate striatal activation. Moreover, the different styles of rotation are inconsistent with the hypothesis that a bias in leg usage sets the direction of turning. Instead, it seems that unilateral striatal activation sets the directionality of turning, independent of any hindlimb motor asymmetries.

Animals↗
PubMed1985

Biphasic modulation of spontaneous activities of entopeduncular neurons by systemic application of apomorphine in anesthetized cats.

The responses of entopeduncular neurons to apomorphine were investigated with extracellular recording methods in anesthetized cats. Apomorphine was applied intravenously in increasing doses, which cumulatively doubled with each addition (5-640 micrograms/kg). The spontaneous firing rates of entopeduncular neurons, which were inhibited by electrical stimulation of the caudate nucleus, increased when lower doses of apomorphine (5-20 micrograms/kg) were applied. However, higher doses (40-640 micrograms/kg) produced a dose-dependent decrease in the firing rate. The results suggest that there are direct and indirect effects of systemically administered apomorphine on entopeduncular neurons which may contribute to biphasic responses in the spontaneous discharge rate.

Action Potentials↗
PubMed1986

Reduced apomorphine sensitivity of dopamine metabolism in rat striatum after repeated administration of methamphetamine.

Rats received daily injections of saline or methamphetamine (MAP; 4 mg/kg/day) for 14 days. Seven days after the completion of this regime, dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured in the striatum following intraperitoneal injections of either saline plus gamma-butyrolactone (GBL; 750 mg/kg) or apomorphine (2 mg/kg) plus GBL. The saline plus GBL challenges produced no difference in the DA or DOPAC levels between saline- and MAP-treated rats. By contrast, the apomorphine plus GBL challenges produced higher DOPAC levels in MAP-treated rats than saline-treated rats, although they produced no difference in the DA levels between the two groups. These results indicate that apomorphine depresses the striatal DA metabolism less in MAP-treated rats than in saline-treated control rats. Repeated MAP administration might produce this effect through apomorphine subsensitivity of presynaptic DA autoreceptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Apomorphine induction of AP-1 DNA binding in the rat striatum after dopamine depletion.

The expression of AP-1 transcription factors was assessed in the dopamine-depleted rat striatum over a 1 week period of repeated apomorphine injections. A single injection of apomorphine increased the expression of a 35 kDa Fos-related antigen and Jun proteins and their expression continued to increase until day 3 of repeated apomorphine treatment in dopamine-depleted striata. Apomorphine induces AP-1 transcription factors which may be involved in modulating gene expression in the striatum.

Animals↗
PubMed1985

Narcotic antagonist potentiation of apomorphine drug effect: a stereospecific, centrally mediated drug action.

Systemic pretreatment with naloxone but not its (+)-enantiomer significantly potentiated apomorphine-induced stereotypic climbing activity in mice. Systemic or central pretreatment with naltrexone also significantly potentiated the apomorphine drug effect. The N-methyl derivative of naltrexone had no influence when administered systemically but significantly potentiated the apomorphine drug effect when administered centrally. These findings suggest that narcotic antagonist potentiation of apomorphine-induced stereotypic climbing in mice is a stereospecific phenomenon that originates in the central nervous system.

Animals↗
PubMed1995

Effects of naloxone on the behaviors evoked by amphetamine and apomorphine in adult cats.

1. This work was undertaken in order to study whether the opioid system is involved in the modulation of the behaviors induced by two agonists of the dopaminergic system, amphetamine and apomorphine in adult cats. 2. Naloxone, an antagonist of the mu, delta and kappa opioid receptors was administered to twelve female mongrel cats; 0.5, 1.0 and 2.0 mg/kg s.c. were injected in order to analyse its own effect of naloxone. This drug produced NREMs behavior and accordingly the cat showed an overall decrease of its activities. 3. Amphetamine (2.5 mg/kg s.c.) and apomorphine (2.0 mg/kg s.c.) were injected before and after naloxone administration (2.0 mg/kg s.c.), in separate sessions. 4. The behaviors recorded were compared. Some of the behaviors showed modifications both with amphetamine (inappetence was increased and locomotion decreased) and apomorphine (indifference and inappetence increased; locomotion and olfaction decreased). 5. These changes were considered as consequence of the NREMs behavior induced by naloxone and not as a result of a modulation by the opioid system of the activation of the dopaminergic system elicited by amphetamine and apomorphine. Regarding the mechanism of NREMs induced by naloxone probably the dopaminergic, noradrenergic and GABAergic systems may be involved.

Amphetamine↗
PubMed1993

A double-blind study of the efficacy of apomorphine and its assessment in 'off'-periods in Parkinson's disease.

Five patients with idiopathic Parkinson's disease with severe response fluctuations were selected for a randomized double-blind placebo-controlled study, concerning the clinical effects of subcutaneous apomorphine and its assessment in 'off'-periods. The study was designed as five n = 1 studies, in which every patient was his own control. The effect of apomorphine was studied by using the Columbia rating scale and quantitative assessments, using tapping, walking and pinboard. There was a significant positive effect of apomorphine, in a mean optimal dose of 2.7 mg, with a mean latency of onset of 7.3 min and a mean duration of response of 96 min. After pretreatment with domperidone, no significant adverse effects were observed. Tapping showed the highest correlation with rigidity and bradykinesia. Walking showed a high correlation with stability and gait. Pinboard testing did not give additional information. The first conclusion was that apomorphine proved to be a significantly effective dopamine agonist, proven now also by a double blind placebo-controlled study. Secondly it was concluded that assessment of clinical effect in parkinsonian patients can be performed best by combining the Columbia item tremor with tapping and walking scores.

Adult↗
PubMed1983

Repeated apomorphine treatment causes behavioural supersensitivity and dopamine D2 receptor hyposensitivity.

This study reports the changes in the behavioural responsiveness of rats in the "Ungerstedt Model' following repeated injections of apomorphine. The changes in striatal [3H]haloperidol binding coincident with the behavioural responses are also estimated. Following unilateral lesions of the substantia nigra, the number of [3H]haloperidol binding sites in the ipsilateral striatum increase, and this effect correlates with the behavioural effect following a single apomorphine injection. Repeated apomorphine treatment, however, results in a decrease of neuroleptic binding sites in the ipsilateral and contralateral striatum accompanied by increased behavioural responses. Thus repeated apomorphine treatment discriminates the receptor mechanisms involved in the behavioural response from those receptors labelled by neuroleptics.

Animals↗
PubMed1988

Dopamine release in the nucleus accumbens of freely moving rats determined by on-line dialysis: effects of apomorphine and the neuroleptic-like peptide desenkephalin-gamma-endorphin.

This study examined the effects of apomorphine, sulpiride, desenkephalin-gamma-endorphin (DE gamma E) and a combination of DE gamma E with apomorphine on the release of dopamine (DA) and its main metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens of freely moving rats. A fully automated on-line brain dialysis system was used. A small dose of s.c. administered apomorphine induced a decrease in the output of DA and DOPAC. Sulpiride, infused into the nucleus accumbens, induced a 2-fold increase in the output of DA, DOPAC and HVA. DE gamma E hardly modified either the basal release of DA, DOPAC and HVA or the apomorphine-induced attenuation of the release of DA and DOPAC. These results indicate a dissociation between the behavioural effects of DE gamma E and its effect on the release of DA in vivo.

Animals↗
PubMed1994

Activation of specific cortical regions by apomorphine: an [15O]H2O PET study in humans.

The purpose of this study was to investigate the functional effects of apomorphine, a non-selective dopamine agonist, on regional neuronal activity using regional cerebral blood flow, measured using [15O]H2O and positron emission tomography (PET), as an index. Eight normal volunteers were scanned twice before and twice after receiving 10 micrograms/kg subcutaneous apomorphine. Apomorphine produced the expected side-effects and endocrine response. Analysis of the PET scans revealed that apomorphine increased regional cerebral blood flow (rCBF), presumably reflecting a change in neuronal activity, in the anterior cingulate, ventral motor cortex and the dorsolateral prefrontal cortex along with a decrease in rCBF in the retrosplenial cingulate region. These regions form a functional network of brain regions modulated by the dopaminergic system.

Adult↗