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 955 records · Page 53Linked to original sources
PubMed1991

Striatal A2 receptor regulates apomorphine-induced turning in rats with unilateral dopamine denervation.

The effect of the purine agonist N-ethylcarboxamido-adenosine (NECA) on apomorphine-induced rotation was investigated in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Intrastriatal administration of NECA on the denervated side caused a dose-dependent inhibition of contralateral rotation. This inhibition was prevented by prior intrastriatal injection of theophylline. The adenosine A1 receptor antagonist 8-cyclopentyltheophylline was ineffective at concentrations which block this receptor, but effective in preventing the action of NECA at concentrations which block the adenosine A2 receptor. In the absence of apomorphine, NECA had no effect on behaviour. It is concluded that A2 receptor activation counteracts apomorphine effects in the striatum. Since the A2 receptor may be localized to striatal cholinergic neurones, the possible role of these neurones in purine-induced behaviours is discussed.

Adenosine↗
PubMed1990

Yawning induced by apomorphine, physostigmine or pilocarpine is potentiated by dihydropyridine calcium channel blockers.

Previous studies have shown that dihydropyridine (DHP) calcium channel blockers can potentiate yawning induced by apomorphine in rats. The present study was undertaken to examine whether or not this interaction was seen with other compounds that induce yawning or if it represented a specific interaction with dopaminergic mechanisms. Yawning induced by apomorphine (40 micrograms/kg SC), physostigmine (50 micrograms/kg SC) or pilocarpine (1 mg/kg SC) was dose-dependently potentiated by the DHP calcium channel blocker nifedipine (1.25-10 mg/kg IP). Nimodipine (1.25-5 mg/kg IP) and nitrendipine (1.25-5 mg/kg IP) also significantly increased the yawning response. The DHP calcium channel blockers alone induced only a low incidence of yawning. The effects of nifedipine on physostigmine-induced yawning were reversed by the DHP calcium channel activator BAY K 8644 which also inhibited yawning induced by physostigmine (100 micrograms/kg SC) and pilocarpine (2 mg/kg SC). In contrast to the DHP compounds, diltiazem (2.5-10 mg/kg IP) and verapamil (2.5-10 mg/kg IP) failed to potentiate yawning. Sulpiride (10 mg/kg SC) antagonised the nifedipine potentiation of apomorphine-induced yawning but not that of physostigmine-induced yawning; atropine (2.5 mg/kg SC) antagonised both effects. These results support the hypothesis that this effect of dihydropyridine compounds is not dependent on, nor mediated through, dopaminergic mechanisms.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2003

Differential sensitivity to acute administration of Ritalin, apomorphine, SCH 23390, but not raclopride in mice selectively bred for hyperactive wheel-running behavior.

RATIONALE: Previous studies of mice ( Mus domesticus) selectively bred for high voluntary wheel running have suggested that the hyperactivity is associated with dysfunction in the dopaminergic neuromodulatory system and that high-running mice may represent a useful genetic model for attention deficit hyperactivity disorder (ADHD). OBJECTIVES: We tested the hypothesis that mice from the four replicate hyperactive lines would respond differently to methylphenidate (Ritalin), apomorphine (non-selective dopamine agonist), SCH 23390 (selective D1-like dopamine antagonist), and raclopride (selective D2-like dopamine antagonist) than individuals from the four replicate, randomly bred, control lines. METHODS: After animals were habituated (3 weeks) to their cages with attached wheels, drugs were administered via intraperitoneal injections, at night, during peak wheel-running activity. Revolutions on wheels 10-70 min post-injection were used to quantify drug responses. RESULTS: Ritalin (15 mg/kg and 30 mg/kg) increased wheel running in control lines but decreased running in selected lines. A low-dose (0.125 mg/kg) of apomorphine reduced wheel running by a similar amount in control and selected lines; however, higher doses of apomorphine (0.25 mg/kg and 0.5 mg/kg) produced greater reductions in wheel running in the control lines. SCH 23390 (0.025, 0.05, and 0.1 mg/kg) caused greater reductions in wheel running in control than in selected lines. Raclopride (0.5, 1, and 2 mg/kg) reduced wheel running by a similar amount in control and selected lines. CONCLUSIONS: These results support the interpretation that genetically determined hyperactive wheel-running behavior is associated with altered dopaminergic function in this mouse model. More specifically, results suggest that D1-like (D1 or D5), but not D2-like (D2, D3, or D4), dopamine receptors have reduced function in the high-running mice. The fact that Ritalin decreased wheel running in selected lines further supports their use as an animal model of ADHD.

Animals↗
PubMed2005

Apomorphine effects on emotional modulation of the startle reflex in rats.

RATIONALE: Emotional modulation of the startle reflex in the rat may be used to assess whether activation of dopamine receptors specifically increases hedonia, incentive, fear or arousal. OBJECTIVES: The objective of the study is to determine the effects of apomorphine (0.8 mg/kg s.c.) on the startle reflex of rats (72 male Sprague-Dawley rats) exposed to one of three affective conditions. These conditions were negative affective stimulus (exposure to cat smell), positive affective stimulus (availability of a 20% sucrose solution), neutral stimulus (no additional affective stimulus) and one of two appetitive "drive" states (food deprived or non-food deprived). METHODS: The startle response (whole-body flinch response) was measured after presentation of a range of intensities of acoustic stimuli (65-120 dB, 40-ms duration white noise). The resulting sigmoidal stimulus intensity-response magnitude (SIRM) curves were fitted using a logistic regression procedure, and features of these functions were abstracted for analysis. RESULTS: Maximal startle amplitudes were increased by the negative affect (fear) stimulus in non-food-deprived rats and decreased by the positive affect stimulus in food-deprived rats. Apomorphine mimicked the effects of food deprivation under both affect conditions, but also produced an effect in food-deprived rats similar to that of the positive affect condition. CONCLUSIONS: The results are consistent with both a positive incentive effect and a direct hedonic action of apomorphine, but inconsistent with a role in general arousal. In addition, a method of analysing SIRM functions with logistic regressions is introduced as a useful means of standardising startle reflex measurements.

Acoustic Stimulation↗
PubMed1998

Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition.

Recent evidence suggests that the dopamine D4 receptor may play a role in schizophrenia, and that the atypical properties of the antipsychotic clozapine may be attributable in part to its antagonistic actions at this receptor. In the present study, clozapine and three other compounds having D4 dopamine receptor antagonist properties were examined for their effectiveness in reducing losses in prepulse inhibition (PPI) induced in rats by the dopamine receptor agonist apomorphine. Previously, activity in the PPI model has been shown to correlate highly with the antipsychotic potency of a number of neuroleptics. As previously reported, clozapine (1-5.6 mg/kg) significantly reduced apomorphine-induced PPI deficits. The three D4-selective compounds, CP-293,019 (5.6-17.8 mg/kg), U-101,387 (3-30 mg/kg) and L-745,870 (1-10 mg/kg), also significantly blocked the losses in PPI produced by apomorphine. Taken together, these results suggest that dopamine receptor antagonists with selectivity for the D4 dopamine receptor subtype may be effective in the treatment of schizophrenia, while being less likely to produce dyskinesias associated with D2 receptor antagonists.

Animals↗
PubMed1998

Mirtazapine enhances the effect of haloperidol on apomorphine-induced climbing behaviour in mice and attenuates haloperidol-induced catalepsy in rats.

Activation of 5-HT1A receptors has been shown to attenuate catalepsy induced by typical antipsychotic compounds. Since mirtazapine (Remeron; Org 3770) has indirect 5-HT1A receptor stimulating properties as well as antagonist properties at alpha2-adrenoceptors and 5-HT2 receptors, it was of interest to investigate how the compound could modulate the effect of haloperidol on apomorphine-induced climbing behaviour in mice and haloperidol-induced catalepsy in rats. In the apomorphine climbing test, it was found that mirtazapine (2.2-22 mg/kg) did not change the climbing behaviour of mice induced by 1 mg/kg of apomorphine. However, when given as a co-treatment with haloperidol, mirtazapine (1 and 10 mg/kg) dose-dependently augmented the inhibiting effect of haloperidol on this climbing behaviour. Co-treatment with the 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) also augmented the effect of haloperidol. Catalepsy induced by haloperidol (4.6 mg/kg) was attenuated by mirtazapine (2.2-22 mg/kg). The strongest effect was seen at 90 min after haloperidol treatment. The results obtained in these experiments suggest that co-treatment with mirtazapine may enhance the antipsychotic effect of haloperidol and reduce its extrapyramidal side effects, thereby widening its therapeutic window.

Animals↗
PubMed2001

Non-monotonic dependency of PPI on temporal parameters: differential alteration by ketamine and MK-801 as opposed to apomorphine and DOI.

RATIONALE: Prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating, is a time-linked phenomenon which depends on prepulse duration (PD) and prepulse-pulse interval (PP). Rats treated with dopaminergic agonists, serotoninergic agonists or glutamatergic antagonists are commonly used as models for the deficit in PPI observed in schizophrenic patients. An important question was whether there is a parametric specificity for the effects of such pharmacological agents. OBJECTIVE: We investigated the contribution of PD, PP, and then of ratio R (PD:PP) to the expression of PPI and we looked for a modification of the temporal dependency of PPI by either apomorphine, DOI, ketamine and/or MK-801. METHODS: Male Sprague-Dawley rats were used. The values used to test PD varied from 5 to 1280 ms, with PP being fixed at 20 ms and vice versa to test PP. Different ratios were used to test R. The effect of either apomorphine (0.5 mg/kg), DOI (1 mg/kg), ketamine (1.5-6 mg/kg) or MK-801 (0.1-0.5 mg/kg) was compared to their vehicle. RESULTS: PPI was a non-monotonic function of each parameter tested. The functions of PD and PP differed. All drugs reduced PPI in each parameter. The shape of the function obtained by varying PD was modified by ketamine and MK-801, but not by apomorphine or DOI. CONCLUSIONS: The specific effect of ketamine and MK-801 was discussed in relation to the hypotheses about the mechanism underlying the modulation of PPI by temporal parameters. These findings stress the importance of non-competitive NMDA antagonist-induced disruption of PPI as a model of the sensorimotor gating deficit observed in schizophrenic patients.

Acoustic Stimulation↗
PubMed1999

The effect of a subchronic post-lesion treatment with (-)-deprenyl on the sensitivity of 6-OHDA-lesioned rats to apomorphine and d-amphetamine.

The effects of a subchronic post-lesion treatment of 14 days with (-)-deprenyl or its solvent on the rotational response to apomorphine (0.1 mg/kg) and d-amphetamine (2.5 mg/kg) in 6-OHDA- and SHAM-lesioned rats were investigated. Rats received a local injection of 6-OHDA (9 microg/0.7 microl) or its solvent into the medial forebrain bundle. Following the (SHAM or 6-OHDA) lesion the animals were randomly assigned to one of the two post-lesion treatment groups, viz. vehicle or (-)-deprenyl (0.1 mg/kg, 2 x day, i.p.) and treated for 14 days. After a wash out period of 6 weeks the number of rotations in response to apomorphine (0.1 mg/kg) and d-amphetamine (2.5 mg/kg) were compared. Seven days following the final behavioural experiments the animals were sacrificed and the striatal dopamine, DOPAC and HVA levels were determined. The (-)-deprenyl-treated 6-OHDA-lesioned rats responded with a reduced number of rotations in response to apomorphine but not to d-amphetamine as compared to vehicle-treated 6-OHDA-lesioned rats. However the two lesion groups did not differ in striatal dopamine, DOPAC and HVA concentrations; the levels were below or close to the detection limit ipsilateral to the 6-OHDA injections. Thus a post-lesion treatment with (-)-deprenyl reduced the dopaminergic supersensitivity without a concomitant increase in striatal dopamine content. The data are discussed in the light of the previously described neurorescue properties of (-)-deprenyl.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson's disease.

The aim of this study was to assess whether patients with Parkinson's disease (PD) develop cognitive and psychiatric complications more frequently during prolonged therapy with continuous apomorphine infusion compared with standard oral treatment. Thirty consecutive PD patients with severe motor fluctuations were included in the study. Twelve patients accepted the treatment with subcutaneous continuous apomorphine infusion, while the remaining 18 preferred to continue with oral dopaminergic therapy. The two groups were evaluated with neuropsychological, psychiatric, and motor tests at baseline and after 1 year. The off daily duration and the levodopa dosage were significantly reduced in infused patients. The neuropsychiatric assessment did not change in both groups compared with baseline, except for a significant improvement of mood in the apomorphine group.

Aged↗
PubMed1992

Suicidal behavior and growth hormone response to apomorphine test.

Several cerebrospinal fluid (CSF) studies have provided support for a possible role for the dopaminergic system as a biological correlate of suicidal behavior. Indeed, low CSF levels of the dopamine metabolite homovanillic acid (HVA) have been described in depressed patients with a history of suicide attempts. In this study, we assessed the dopamine receptor sensitivity in relationship to suicidal behavior by measuring growth hormone (GH) response to apomorphine 0.5 mg subcutaneously (sc) in 15 DSM-III-R (APA 1987) major depressive inpatients with a history of suicide attempts, compared to age-matched and gender-matched major depressive inpatients without a history of suicide. Patients with a history of suicidal behavior exhibited a significantly lower GH response to apomorphine than patients who never attempted suicide (t = 3.60, df = 1.28, p = 0.0012). Therefore, these results suggest that a blunted GH response to apomorphine could represent a biological marker of suicidal behavior.

Adult↗
PubMed1995

Prefrontal cortical and hippocampal modulation of haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors in the rat.

Effects of prefrontal cortical or hippocampal excitotoxic lesions on behavioral parameters related to dopaminergic transmission in the basal ganglia were investigated in the rat. We examined haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors after ibotenic acid lesions of the medial prefrontal cortex (MPFC), dorsal (DH), or ventral hippocampus (VH) in adult rats. Haloperidol-induced (1 mg/kg) catalepsy was decreased in rats with either MPFC or VH but not DH lesions. While both DH and VH lesioned animals demonstrated a reduction in apomorphine-induced (0.75 mg/kg) stereotypic behaviors, the VH lesioned animals also showed an enhancement of locomotor activity. MPFC lesioned rats tended towards potentiation of stereotypic behaviors and reduced locomotion after apomorphine administration. These data indicate that loss of prefrontal cortical or hippocampal modulation leads to an enhancement of DA transmission within the basal ganglia, though the pattern of augmentation depends on the area lesioned.

Animals↗
PubMed1976

Interactions of nigrostriate synaptic transmission, iontophoretic O-methylated phenethylamines, dopamine, apomorphine and acetylcholine.

Recordings were made from, and drugs applied to, neurons in the caudate nucleus of unanesthetized cats, using multibarrel micropipette electrodes. The substantia nigra was stimulated by sterotactically placed electrodes. Three O-methylated derivatives of dopamine, meta-methoxyphenethylamine (m-MPEA), para-methosy-phenethylamine (p-MPEA) and 3,4-demethoxyphenethylamine (DIMPEA), inhibited most, excited a few, and had no detectable effect on a substantial number of the cells upon which they were tested. A statistically significant correlation was found between the effects of dopamine (DA) and the three O-methylated derivatives on the same populations of cells. Iontophoretic release of the O-methylated derivatives could not prevent the actions of DA, nor could it block synaptically mediated effects of the nigrostriate pathway. It is concluded that the three O-methylated products are partial agonists of DA. The findings are difficult to reconcile with the suggestion that the experimental parkinsonian-like symptoms caused by O-methylated phenethylamines are the consequence of blockade of dopaminergic synapses. No correlation, negative or positive, was found between the effects of DA and of acetylcholine (ACh). The findings do not support the theory that balanced sets of antagonistic synapses, one dopaminergic, the other cholinervic, operate upon individual neurons in the caudate nucleus. Apomorphine and dopamine were shown to have similar effects on a substantial number of neurons, even though the onset and offset of the effect of apomorphine were slower than those of DA. This observation agrees with the suggestion that some of the central effects of apomorphine are due to an action at dopaminoceptive receptor sites.

Acetylcholine↗
PubMed1981

Changes in dopamine and DOPAC following systemic administration of apomorphine and 3,4-dihydroxyphenylamino-2-imidazoline (DPI) in rats.

Rats were injected systemically with either saline, apomorphine, or one of four doses of DPI (3,4-dihydroxyphenylamino-2-imidazoline) and the levels of dopamine and DOPAC determined in the nucleus accumbens and the caudate regions. DPI reduced dopamine and DOPAC levels in the nucleus accumbens, while apomorphine did not. On the other hand, apomorphine reduced the levels of dopamine and DOPAC in the caudate but not the nucleus accumbens. DPI largely was without effect in the caudate. The results are discussed in terms of possible specificity of the two dopamine agonists in the two forebrain regions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Apomorphine-induced changes in local cerebral blood flow in normal rats and after lesions of the dopaminergic nigrostriatal bundle.

Systemic administration of the dopamine (DA) receptor agonist apomorphine leads to a general increase in cerebral blood flow (CBF) as determined by the autoradiographic iodoantipyrine technique. The magnitude of the increase varies between different regions but shows no obvious relation to the density of either DA terminals or receptors. The circulatory response is much more prominent in the lateral than in the medial caudate-putamen. Apomorphine seems to increase CBF both via a change in metabolic rate and via stimulation of dilatory vascular receptors. In animals with unilateral 6-hydroxydopamine lesions of the ascending DA pathways apomorphine induces an augmented CBF response in some denervated structures, notably caudate-putamen and globus pallidus. It is concluded that this is partly due to stimulation of denervated supersensitive vascular receptors, suggesting a direct dopaminergic control of the blood vessels in these areas.

Animals↗
PubMed1984

Lithium attenuates the development of lesion-induced behavioral supersensitivity to apomorphine.

The unilateral nigrostriatal lesion preparation was used to examine the effect of long-term treatment with lithium on rotation in response to the dopamine agonists apomorphine and amphetamine. Rats with unilateral striatal denervation received daily injections of either lithium chloride or saline for 14 days, beginning 24 h after surgery. Rats treated with lithium showed a reversible reduction in apomorphine-induced contralateral rotation. Lithium treatment failed to substantially alter amphetamine-induced ipsilateral rotation. When treatment was initiated 14 days after surgery, rats treated with lithium showed no reduction in apomorphine-induced contralateral rotation. These findings suggest that lithium attenuates the development of lesion-induced behavioral supersensitivity but fails to alter supersensitivity which has developed previously.

Animals↗
PubMed1984

Local cerebral glucose utilization altered in rats with unilateral electrolytic striatal lesions and modification by apomorphine.

Alterations in local cerebral glucose utilization (LCGU) in rats with unilateral striatal lesions and the modification by apomorphine were investigated. Electrolytic lesions were made in the rostral part of the right striatum, and 1, 7, and 30 days later, LCGU was observed in terms of relative and absolute LCGU values, using the [14C]deoxyglucose method. A definite change in the pattern of LCGU was seen only at 7 days. These were increases in LCGU in the globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata, and decreases in the ventroanterior-ventrolateral (VAL) and ventromedial (VM) thalamic nuclei and lateral habenula, all on the lesioned side. The circling behavior following the lesion, however, was maximal after 2 days and disappeared after 7 days. Intravenous administration of apomorphine (1.5 mg/kg) produced different modifications in the LCGU pattern between the intact and lesioned sides, at 7 days after producing the lesions. On the intact side, there were increases in LCGU in the striatum, globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata and subthalamic nucleus, and a decrease in the lateral habenula. No such changes were observed on the lesioned side. These results indicate firstly that electrolytic striatal lesions induce LCGU increases or decreases in the structures which receive the striatal input, secondly that the mechanism of this change differs from that of the circling behavior seen in case of striatal lesions, and finally that the majority of the LCGU changes in the basal ganglia and thalamus following intravenous administration of apomorphine are brought about by an altered input of neuronal activity from the striatum to these structures.

Animals↗
PubMed1984

Nigral dopaminergic neurons: differential sensitivity to apomorphine following long-term treatment with low and high doses of amphetamine.

Twice daily injections of 1.0 or 5.0 mg/kg D-amphetamine for 6 consecutive days differentially affected the response of dopaminergic neurons in the substantia nigra pars compacta to challenge injections of apomorphine on the following day. Thus, whereas treatment with the high amphetamine dose produced a dramatic shift to the right of the apomorphine dose-response curve, rats treated with 1.0 mg/kg D-amphetamine responded to apomorphine in the same way as saline-treated controls. These results support the view that long-term treatment with relatively high amphetamine doses is required to produce autoreceptor subsensitivity in the substantia nigra.

Animals↗
PubMed1987

Paraventricular nucleus lesion prevents yawning and penile erection induced by apomorphine and oxytocin but not by ACTH in rats.

The effect of electrolytic lesion of the paraventricular nucleus of the hypothalamus (PVN) on yawning and penile erection induced by apomorphine, oxytocin and adrenocorticotropic hormone (ACTH1-24) was studied in male rats. In sham-operated rats, apomorphine (50 micrograms/kg s.c.), oxytocin (30 ng i.c.v.), and ACTH1-24 (10 micrograms i.c.v.) significantly increased the number of yawning and penile erection episodes. In PVN-lesioned rats, apomorphine- and oxytocin-, but not ACTH-induced responses were strongly reduced. These results confirm our previous observations showing that the PVN has a crucial role in the expression of yawning and penile erection induced by dopamino-mimetic drugs and oxytocin, and suggest that ACTH-derived peptides induce the above responses by a mechanism not involving PVN hypothalamic dopamine or oxytocin.

Adrenocorticotropic Hormone↗