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 703 records · Page 39Linked to original sources
PubMed1995

Intrastriatal injection of opioid receptor agonists inhibits apomorphine-induced behavior in 6-hydroxydopamine-treated mice.

The effects of intrastriatal (i.st.) injections of mu-, delta-, and kappa-selective opioid receptor agonists on the augmentation of apomorphine-induced behaviors were determined in 6-hydroxydopamine-treated mice by using multidimensional behavioral analyses. 6-Hydroxydopamine (16 mu g/mu l, i.st.) was unilaterally injected into the striatum 30 min after pretreatment with desipramine (25 mg/kg, s.c). Mice were tested 14 days after injection of 6-hydroxydopamine. Apomorphine (0.5 mg/kg, s.c.) produced a marked increase in linear locomotion, contralateral circling and/or rearing behavior in 6-hydroxydopamine- but not vehicle-treated mice. Although the mu-selective opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) (0.1 and 0.3 ng, i.st.) or the kappa-selective opioid agonist dynorphin A-(1-13) (0.1 and 0.3 mu g, i.st.) did not produce any significant effects on behavior, these peptides had an inhibitory effect on the apomorphine (0.5 mg/kg, s.c.)-induced increase in behavioral responses such as linear locomotion, contralateral circling and/or rearing behavior in 6-hydroxydopamine-treated mice. The inhibitory effects of DAMGO (0.3 ng, i.st.) and dynorphin A-(1-13) (0.3 mu g, i.st.) were fully reversed by selective opioid receptor antagonists such as beta-funaltrexamine (5 mu g, i.c.v.) and (--)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7-benzomorph an (Mr2266) (10 mg/kg, s.c.), respectively. In contrast, the delta-selective opioid receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (0.03, 0.1 or 0.3 mu g, i.st.) had no marked effects on the apomorphine (0.5 mg/kg, s.c.)-induced behavior in 6-hydroxydopamine-treated mice. These results suggest that the stimulation of mu- and kappa- but not delta-opioid receptors plays an inhibitory role in the behavioral augmentation induced by the activation of postsynaptic dopamine receptors in the striatum sensitized with 6-hydroxydopamine.

Animals↗
PubMed1986

Apomorphine has a therapeutic effect on neglect produced by unilateral dorsomedial prefrontal cortex lesions in rats.

Neglect is a disorder in which the response to stimulation is diminished or absent on the side of the body contralateral to the lesion in the absence of an elemental sensory or motor defect. Most cases of neglect in humans are induced by cortical damage, but there have been no investigations of the pharmacologic basis of neglect induced by cortical damage. We examined the role of the dopamine system in polymodal neglect caused by a unilateral lesion of the medial precentral prefrontal cortex of the rat. A dose-response examination of the effect of apomorphine on neglect revealed that apomorphine, at 0.5 mg/kg, the highest dose examined, significantly improved the orientation scores of subjects in all modalities tested and significantly decreased the total number of allesthetic responses. The therapeutic effect of apomorphine was mediated by dopamine receptors as the therapeutic effect of apomorphine was blocked by prior administration of spiroperidol. These results demonstrate the important role of disruption of dopamine mechanisms in neglect induced by a lesion of medial precentral cortex.

Animals↗
PubMed1988

The deafferentation syndrome in the rat: effects of intraventricular apomorphine.

A deafferentation syndrome, produced in rats by dorsal root ganglionectomies, is expressed as scratching of partially deafferented limb areas and/or biting of anesthetic limb areas. This self-mutilation may be objective evidence of dysesthesias, thus serving as an experimental model to study chronic dysesthesias and/or pain from deafferentation in man. This study included behavioral observations of the syndrome and the effects of intraventricular apomorphine, a dopamine agonist, on its expression. Thirty-eight female Sprague-Dawley rats underwent unilateral C5-T2 dorsal root ganglionectomies followed immediately by stereotactically guided cannulation of the right lateral ventricle in 20 of the rats. For 2 weeks continuously via an osmotic minipump, 10 rats received apomorphine (5 micrograms/h) and 10 others received L-ascorbate (the vehicle). Rats with ganglionectomies only, as well as those receiving L-ascorbate, demonstrated early onset, more severe and later onset, less severe biting groups (P less than 0.05 Mann-Whitney U). Animals receiving apomorphine exhibited low autotomy scores irrespective of time of bite onset. Among the control groups, but not the experimental animals, the earlier the onset of biting, the more severe was the autotomy. The rats receiving vehicle via the minipump had earlier bite onsets than the rats in the ganglionectomy only group. This may indicate that the presence of the minipump is a stress which can accelerate the onset of biting. Intraventricular apomorphine can affect the deafferentation syndrome in the rat; it seems to decrease the level of autotomy and disrupt the relationship of bite onset with degree of biting.

Afferent Pathways↗
PubMed1982

Chronic haloperidol treatment potentiates apomorphine- and ethanol-induced hypothermia in the rat.

Supersensitivity developed in the central dopaminergic system of the rat after 21 days of chronic haloperidol injection. This was indicated by a higher level of apomorphine-elicited stereotypic behavior and by higher concentrations of striatal 3H-spiroperidol binding sites in haloperidol-treated rats compared to saline-treated controls. The chronic haloperidol treatment did not affect the baseline body temperature but potentiated both apomorphine- and ethanol-induced falls in core temperature. Such potentiation may also be related to dopamine supersensitivity. However, no significant correlation was found between apomorphine- or ethanol-induced hypothermia and apomorphine-elicited stereotypic behavior or the concentration of striatal 3H-spiroperidol binding sites. Hence, the nigrostriatal dopamine system does not appear to be involved in the development of hypothermic responses to these agents.

Animals↗
PubMed1985

Subchronic methamphetamine treatment selectively attenuates apomorphine-induced decrease in 3,4-dihydroxyphenylacetic acid level in mesolimbic dopaminergic regions.

To investigate mechanisms of behavioral enhancement produced by repeated doses of amphetamines, the effects of apomorphine on 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) levels were examined in various brain regions of the rat on the 4th day of withdrawal after repeated administration of saline or methamphetamine (3 mg/kg, s.c.) twice daily for 14 days. Apomorphine (0.1 and 1.0 mg/kg, i.p.) produced a dose-dependent decrease in DOPAC levels and no effect on DA levels in the olfactory tubercle, nucleus accumbens, striatum, frontal and cingulate cortices of saline-treated animals. A decrease in DOPAC levels produced by a low dose of apomorphine was attenuated selectively in the olfactory tubercle and nucleus accumbens of methamphetamine-treated animals. A high dose of apomorphine produced a significant decrease in DOPAC levels in both regions. No such attenuation was obtained in the striatum and the frontal and cingulate cortices. These results suggest that subchronic methamphetamine may induce development of hyposensitivity of presynaptic DA receptors in the mesolimbic regions, which contribute to the behavioral enhancement produced by the drug.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Conditioned response to apomorphine in nigro-striatal system-lesioned rats: the origin of undrugged rotational response.

Development and time-course characteristics of Early rotational response (ER) to apomorphine in 6-hydroxydopamine-lesioned rats is explored. We show here how this ER can be considered a conditioned response that arises when the drug is repeatedly administered, according to a classical conditioning paradigm. In this way, the ER to apomorphine can be considered a non-pharmacological, conditioned, placebo response, the drug action being the unconditioned stimulus (UCS). In our model, the undrugged rotational response elicited by saline injections two weeks after drug treatment can be considered as the conditioned response (CR) to the conditioned stimulus, the CS being the environment associated with the drug treatment. This CR had not previously been identified during the drug treatment. Thus, we studied the acquisition of the ER, nonexistent after the first injection of apomorphine. Furthermore, we distinguish between this ER and the later, strictly pharmacological rotational response (LR) to apomorphine. Finally, we related this ER to the undrugged, paradoxical response to saline. In conclusion, we demonstrate the paradigm of pharmacological conditioning using this animal model of Parkinson's disease, supported by our own results and those of Silverman and Ho (1981).

Animals↗
PubMed1988

Presynaptic inhibition of nigrostriatal dopamine release in the mouse: lack of cross tolerance between apomorphine, GBL and CGS 10746B.

Acute parenteral injections of apomorphine, gamma-butyrolactone (GBL) and CGS 10746B decreased dopamine release in the mouse nigrostriatal pathway as evidenced by decreases in striatal 3-methoxytyramine levels. In a 7 day treatment paradigm, the effects of acute apomorphine, GBL and CGS 10746B were unaltered in animals treated b.i.d. with GBL (500 mg/kg, i.p.). In contrast, the actions of acute CGS 10746B expressed a complete tolerance in mice treated b.i.d. with CGS 10746B (20 mg/kg, i.p.), while the actions of acute apomorphine or GBL were similar in the chronic saline and chronic CGS 10746 groups. These data show that the inhibition of striatal dopamine release by CGS 10746B is susceptible to tolerance. In addition, the lack of cross tolerance between GBL, apomorphine and CGS 10746B suggests independent sites of action for these agents in inhibiting dopamine release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

The effects of estrogen on apomorphine-induced hypothermia and stereotypy in the rat.

The effects of various doses of estrogen on apomorphine (Apo)-induced hypothermia and stereotypy were investigated in ovariectomized rats. Daily administration of estradiol (5, 15 or 100 micrograms/kg) for 4 days or estradiol (100 micrograms/kg) for 3 days, followed by 4 and 72 hr withdrawal periods respectively, had no effect on apomorphine-induced hypothermia or stereotypy in a cold (4 degrees C) environment, although both effects were blocked by haloperidol. Large doses of estradiol (100 micrograms/kg) given for 3 days, followed by either 24 or 72 hr withdrawal, slightly attenuated apomorphine-induced stereotypy at 22 degrees C. Stereotypy observed at 22 degrees C was of greater magnitude than that seen at 4 degrees C. The results indicate that although high, non-physiological levels of estrogen may attenuate striatal-dependent stereotypies, this hormone has no detectable influence on dopaminergic mechanisms in the preoptic-anterior hypothalamic regions that are thought to mediate apomorphine-induced hypothermia.

Animals↗
PubMed1984

Effects of cholecystokinin on apomorphine-induced changes of motility in rats.

Subcutaneous injection of apomorphine in small doses decreased, while larger doses increased motility in rats. The hypomotility was abolished by intracerebroventricular administration of sulphated cholecystokinin octapeptide [CCK-8(s)], but not by non-sulphated CCK-8 [CCK-8(ns)]. In contrast, the hypermotility was not influenced by CCK peptides. An antiserum directed against the C-terminus of CCK did not affect hypermotility induced by apomorphine but suppressed the apomorphine-induced hypomotility further. The results indicate that sulphated CCK-peptides contribute to the control of motility, which can be inhibited by apomorphine.

Animals↗
PubMed1984

Apomorphine-induced inhibition of neostriatal activity is enhanced by lesions induced by 6-hydroxydopamine but not by long-term administration of amphetamine.

Single-unit activity was recorded in the neostriatum of locally-anesthetized, immobilized rats which had received either a unilateral injection of 6-hydroxydopamine (6-OHDA) into the nigro-neostriatal dopamine pathway, or repeated injections (twice daily for 6 days) of saline, 1.0, 5.0 or 10.0 mg/kg (+)-amphetamine. A staircase regimen of apomorphine was administered intravenously to each rat to determine if the long-term administration of amphetamine changed the sensitivity of postsynaptic dopamine receptors in a way comparable to that produced by 6-hydroxydopamine. In all groups, the most frequent response to apomorphine was inhibition of neostriatal activity. In saline-treated rats, most units were moderately excited by small doses of apomorphine (0.0025-0.02 mg/kg) and then inhibited by doses exceeding 0.04 mg/kg. In rats with lesions induced by 6-hydroxydopamine, apomorphine caused significantly more inhibition than in saline-treated animals. By contrast, neuronal responses in amphetamine-treated rats were not significantly different from those of saline controls. These results indicate that the long-term administration of amphetamine produces an augmentation of behavior by some mechanism other than an increase in the sensitivity of postsynaptic dopamine receptors.

Action Potentials↗
PubMed1986

Effect of chronic administration of alprazolam and adinazolam on clonidine- or apomorphine-induced aggression in laboratory rodents.

The activity of chronic (3 weeks) treatment with the triazolobenzodiazepines, alprazolam and adinazolam, on clonidine- and apomorphine-induced aggression were studied. Adinazolam, like desipramine, potentiated aggression induced by clonidine while diazepam and alprazolam completely abolished it. In the apomorphine-induced aggression, adinazolam suppressed both aggressivity and stereotypy, while diazepam slightly potentiated it. Alprazolam did not modify the effect of aggression induced by apomorphine. On the whole, while adinazolam seemed to develop an activity closer to that of a classical antidepressant like desipramine, alprazolam appeared to be more similar to the benzodiazepines on clonidine-induced aggression in mice. Compared to desipramine and diazepam, adinazolam left these two effects induced by apomorphine almost unchanged. The experiments performed showed differences between the profiles of action of the two triazolobenzodiazepines studied.

Aggression↗
PubMed1987

Effects of apomorphine and (+/-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine, injected into the striatum, on the caudate spindle in the rat.

The caudate spindle in rats was observed following bilateral application of apomorphine (1.5-50 micrograms) and (+/-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP, 0.3-3 micrograms) into the striatum. The smallest dose (1.5 micrograms) of apomorphine enhanced the spindle whereas with a larger dose (50 micrograms), suppression occurred. The preferential dopamine (DA) autoreceptor (inhibitory-receptor) agonist, (+/-)-3-PPP, enhanced the spindle, in a dose-dependent manner. The enhancing effect of apomorphine (1.5 micrograms) and (+/-)-3-PPP (3 micrograms) was prevented by neuroleptics, such as haloperidol (20 micrograms/kg, i.v.) and sulpiride (2 mg/kg, i.v.) at doses which, per se, did not affect the spindle. Small doses of neuroleptics are thought to block DA autoreceptors, suggesting that the enhancing effects of the DA agonists are mediated by autoreceptors. These results lend further support to the assumption that the development of the caudate spindle involves activation or DA receptors. Enhancement of the spindle, induced by injections of apomorphine into the striatum (small dose) and (+/-)-3-PPP, may be mediated by DA autoreceptors (inhibitory-receptors) located at presynaptic elements of the nigro-striatal DA system, while suppression may be due to stimulation of the postsynaptic DA receptors.

Animals↗
PubMed1988

Effects of apomorphine in quantified electroencephalography in the frontal cortex: changes with dose and time.

The purpose of this study was to investigate the role of four doses of apomorphine (0.01, 0.05, 0.25, 1 mg/kg s.c.) on the cortical activity by a quantified electroencephalography (EEG) method recently developed in our laboratory. The EEG-effects of apomorphine were changed significantly according to the dose and the time. When initial effects were considered an opposition in the apomorphine-induced variations between low (0.01 mg/kg) and higher doses were observed. In the time course with 0.01, 0.25 and 1 mg/kg SC, EEG variations changed the direction in 6-17 Hz and diminished in the other spectral components. Qualitatively, this tardive change with 0.01 mg/kg may show a feed-back response of the dopaminergic system to the initial low dose-induced depressant effects of apomorphine. On the other hand higher doses-induced tardive EEG pattern may show a possible changed balance in the stimulated D1 and D2 receptors.

Animals↗
PubMed1988

Comparison between apomorphine and amphetamine-induced rotational behaviour in rats with a unilateral nigrostriatal pathway lesion.

Apomorphine and amphetamine-induced rotational behaviour in 310 rats with a unilateral 6-OHDA nigrostriatal pathway lesion has been studied. Animals presenting an apomorphine-induced contralateral rotation with a "two-peak" pattern, showed a greater number of contralateral turns induced by apomorphine and fewer ipsilateral turns induced by amphetamine than rats without this pattern. In addition, we have not found any correlation between apomorphine and amphetamine-induced turning behaviour.

Amphetamine↗
PubMed1989

Potentiation of apomorphine-induced stereotyped behaviour by acute treatment with dopamine depleting agents: a potential role for an increased stimulation of D1 dopamine receptors.

Treatment of mice with reserpine (10 mg/kg, s.c.) and alpha-methylparatyrosine (400 mg/kg) led to the potentiation of stereotyped behaviour, induced by apomorphine (0.37-1.5 mg/kg, s.c.), i.e. to the appearance of licking and gnawing in addition to climbing and sniffing occurring in control mice. Similar results were obtained by combined treatment with SK&F 38393 (30 mg/kg, s.c.) and RU 24926 (15 mg/kg, i.p.). In mice treated with dopamine depleting agents, SCH 23390 (1.25-20 micrograms/kg, s.c.) and metoclopramide (0.62-20 mg/kg, i.p.) antagonized gnawing induced by 0.75 mg/kg (s.c.) apomorphine, at doses significantly larger than those required for the antagonism of climbing and sniffing. The same treatment with reserpine and alpha-methylparatyrosine produced an increased formation of cyclic AMP, induced by SK&F 38393 (10(-8)-10(-4) M), from homogenates of the striatum of the rat. Potentiation of apomorphine-induced stereotyped behaviour and increased SK&F 38393-induced formation of cyclic AMP had similar time-courses with a maximum 18 hr after treatment. These data suggest that the potentiation of apomorphine-induced stereotyped behaviour produced by acute treatment with dopamine depleting agents is at least partly due to an increased activity of the adenylate cyclase linked to D1 dopamine receptors. Finally, a small dose of amisulpride (a discriminant benzamide derivative) potentiated the stereotyped behaviour induced by the combined treatment with SK&F 38393 and RU 24926 in naive mice and, in a more marked manner, in mice treated with dopamine depleting agents; amisulpride did not produce stereotyped behaviour when combined with SK&F 38393 or RU 24926 administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1976

Actions of repeated injections of LSD and apomorphine on the copulatory response of female rats.

LSD, a serotonin receptor stimulating agent, inhibits copulatory behavior (lordosis response) in the ovariectomized and estrogen + progesterone treated female rat. The same effect is obtained by apomorphine, a dopamine receptor stimulating compounds. The lordosis has been shown to be dependent on serotonin, but also dopamine has been implicated in its mediation. Tolerance develops to certain responses after repeated injections of LSD and in the present study the influence of apomorphine and LSD was compared, when given in repeated doses. Possible cross-tolerance between the two compounds was also tested on the frequency of lordosis responding in ovariectomized and hormone treated female rats. Tolerance to LSD develops over seven days, while the suppressing influence of apomorphine on lordosis in seven repeated doses is not significantly altered from that of a single dose. No cross-tolerance was observed on the lordosis response with either order of treatments. Repeated doses of LSD did not influence locomotor activity differently from a single dose, while repeated doses of apomorphine enhanced this response in comparison with the effect of an acute dose. These results indicate differential sensitivity to the repeated treatments and further support an interpretation of the LSD effects on lordosis responding to be primarily on serotonergic rather than dopaminergic receptors.

Animals↗
PubMed1976

Differentiaton of neuropharmacological actions of apomorphine and d-amphetamine.

The dopaminergic agonists apomorphine and d-amphetamine elicit hyperthermic, hyperkinetic and stereotypic responses in the rabbit. The present investigation compares the influence exerted by various serotonergic antagonists upon these activities. Apomorphine-induced hyperthemia was antagonized by p-chlorophenylalanine (pCPA), cyproheptadine and cinanserin and was restored in pCPA-pretreated rabbits by regeneration of central serotonin levels, d-Amphetamine-induced hyperthermia was reduced by pCPA; restored in pCPA-pretreated animals by regeneration of central serotonin levels; and was uninfluenced by cyproheptadine and cinanserin. Apomorphine-induced locomotor stimulation was unaltered by serotonergic antagonists; however, these same doses of anti-serotonergic agents all markedly reduced d-amphetamine-induced hyperkinesia. Serotonergic antgaonists also failed to affect apomorphine-induced compulsive gnawing but did significantly enhance d-amphetamine-induced compulsive gnawing. It is concluded from these data that the neuropharmacological activities of apopmorphine and d-amphetamine in the rabbit differ in their dependence upon central serotonergic mechanisms.

Animals↗
PubMed1976

Blockade of apomorphine's discriminative stimulus properties: relation to neuroleptic activity in neuropharmacological and biochemical assays.

Using a food-reinforced two-lever operant conditioning procedure, rats were trained to discriminate 0.16 mg/kg apomorphine from saline. Eight neuroleptics of the phenothiazine, butyrophenone or diphenylbutylamine type were investigated for thsir ability to antagonize the discriminative stimulus properties of apomorphine. The same drugs were also assayed for in vivo antagonism of apomorphine-induced stereotyped behavior as well as for in vitro inhibition of stereospecific 3-H-haloperidol binding in rat striatal tissue preparations. The data are consistent with the hypothesis that apomorphine exerts its discriminative stimulus properties by a mechanism similar to that underlying its stereotypogenic action. The loci involved in these two phenomena are likely to be distinct.

Animals↗