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At least 991 records · Page 55Linked to original sources
PubMed1989

MIF-1 attenuates apomorphine stereotypies in adult rats after neonatal 6-hydroxydopamine.

Since prolyl-leucyl-glycinamide (MIF-1) modifies the behavior of adult rats after treatment with neuroleptics, we examined whether MIF-1 would also modify adult behavior after treatment of neonatal rats with 6-hydroxydopamine (6-OHDA). Rats received 6-OHDA (100 micrograms i.c.v.) or diluent at 3 days after birth and either MIF-1 (2.0 mg/kg per day s.c. x 10 days) or diluent beginning at 28 or 29 days after birth. At 5 weeks, a low dose (0.1 mg/kg s.c.) of apomorphine increased the distance traveled, time in ambulation, number of stereotypic movements, and number of movements per time in stereotypy, but decreased the time in stereotypy in the 6-OHDA group. MIF-1 (x 7 or 8 days) showed a tendency to attenuate the increased number of movements and significantly (P less than 0.05) reduced all of the other effects of neonatal 6-OHDA. Behavior induced by higher doses of apomorphine in the 6-OHDA group (reduced licking and head nodding; increased paw treading, taffy pulling and self-biting) were not attenuated by MIF-1. At 38 or 39 days, total in vitro binding of [3H]SCH-23390 and [3H]spiroperidol to striatal homogenates was not altered in any of the groups. The findings demonstrate that specific early developmental alterations in apomorphine-induced behaviors can be modified by treatment of adult rats with MIF-1, even in the absence of overt changes in the binding of striatal dopamine D-1 and D-2 receptors.

Animals↗
PubMed1990

Baseline and apomorphine-induced extracellular levels of nigral substance P are increased in an animal model of Parkinson's disease.

Parkinson's disease arises from extensive premature loss of dopamine (DA)-utilizing midbrain neurons whose axons form the nigrostriatal pathway and densely innervate the striatum (caudate-putamen). The clinical symptoms of Parkinson's disease are improved by treatment with DA receptor agonists, including apomorphine. DA agonists modulate basal ganglia outflow at multiple sites and may affect synaptic activity of multiple basal ganglia neurotransmitters, including substance-P peptide (SP). With microdialysis in the substantia nigra reticulata (s.n.r.), a major striatal projection area, we monitored the extracellular level of SP-like immunoreactivity (SP-LI) in awake rats with neurotoxin-induced destruction of nigral DA neurons, before and after treatment with apomorphine (1 mg/kg i.p.). Loss of DA neurons produced a 60% increase in baseline extracellular SP-LI levels. Apomorphine treatment increased baseline extracellular SP-LI levels up to 60% in control rats and 100% in rats with loss of nigral DA neurons. Striatonigral SP endings increase SP release in response to loss of nigral target DA neurons, and DA agonist acting on supersensitive DA receptors, perhaps on SP terminals in the nigra, further increases synaptic SP concentrations.

Animals↗
PubMed1993

Chronic antidepressant drug treatment attenuates motor-suppressant effects of apomorphine without changing [3H]GBR 12935 binding.

The effects of chronic administration (28 days s.c. via osmotic minipumps) of the antidepressants phenelzine sulphate, desipramine hydrochloride and clomipramine hydrochloride (each at 10 mg/kg per day) on dopamine function have been measured in rats. Both phenelzine and desipramine attenuated the suppression of locomotor activity induced by apomorphine hydrochloride (0.05 mg/kg s.c. 15 min). Clomipramine did not affect the behavioural response to apomorphine. Analyses of brain tissue from these animals using the radioligand [3H]GBR 12935 revealed that there were no changes in dopamine uptake site density or affinity following the administration of phenelzine, desipramine or clomipramine. Analyses of brain monoamine oxidase activity and tricyclic levels were used to confirm the efficacy of the drug administration protocol. These data indicate that changes in dopamine uptake site density do not mediate antidepressant-induced changes in behavioural responses to apomorphine.

Animals↗
PubMed1995

Induction of mating behavior by apomorphine in sexually sated rats.

We have tested the hypothesis, suggested by our previous neurochemical studies, that the inhibition of sexual behavior that follows unrestricted mating could be caused by a blockade of dopaminergic transmission. Male rats were allowed to copulate until they reached a satiety criterion. The following day, after verification that they were sexually inactive, the animals were injected with the dopamine agonist, apomorphine, at doses of 80, 200, and 500 micrograms/kg body weight and their behavior with receptive females was recorded. A bell-shaped dose-response curve was found, with the 200 micrograms/kg dose having the maximal stimulatory effects on mating. Whereas these findings seem to support the above hypothesis, it should be noted that apomorphine treatments were unable to restore fully the copulatory pattern shown by sexually rested animals. This could be due to several factors including the interference of apomorphine-induced stereotypies, and/or the involvement of additional transmitter systems in the mechanisms of sexual satiety.

Animals↗
PubMed1993

Behavioral tolerance to repeated apomorphine administration in parkinsonian monkeys.

Four consecutive injections (s.c.) of apomorphine (Apo) were given to 5 parkinsonian monkeys after i.v. MPTP administration. The minimal effective dose (MED) of Apo was defined as that capable of reducing motor disability by 50% or more for a minimum period of 30 min. Repeated apomorphine injections were given with an interval of 30 min after the motor effect of the previous injection had worn off or with a separation of 3 h between injections. The doses used in different experiments were the MED (2.4 micrograms/kg), 4 MED and 8 MED. In every experiment the duration of motor benefit was longest with the first Apo injection. There was a decay in the duration of the response elicited by consecutive Apo injections when given 30 min after the previous effect had waned. This was significant for the MED and 4 MED (ANOVA, P < 0.01). When Apo boluses were given with an interval of 3 h there was a significant reduction in the duration of the response elicited by the MED, 4 MED and 8 MED of apomorphine. For the MED the reduction in the duration of the motor response was significantly greater for injections given with a 30-min interval than 3-h interval. These findings indicate that behavioral hyposensitivity to repeated Apo administration in parkinsonian monkeys occurs preferentially when near threshold doses are given with short intervals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Simultaneous catalepsy and apomorphine-induced stereotypic behavior in mice.

Intraventricular administration of haloperidol or chlorpromazine produces catalepsy and blocks apomorphine-induced stereotypic behavior. Low intraventricular doses of domperidone, sulpiride and spiperone, equally cataleptogenic as haloperidol or chlorpromazine, augment rather than diminish stereotypic behavior produced by subsequent apomorphine treatment. The resultant stereotypic behavior continues even while the animal is in a rigid cataleptic posture and is marked by persistent gnawing and licking. Prior to the induction of catalepsy and after recovery from it, mice display the entire range of typical apomorphine-induced behavior including sniffing, climbing, gnawing, and licking. This animal model may be related to the clinical observation of the coexistence of tardive dyskinesia and drug-induced Parkinsonism in individual patients.

Animals↗
PubMed1992

Apomorphine-induced changes in striatal and pallidal neuronal activity are modified by NMDA and muscarinic receptor blockade.

Systemic administration of apomorphine decreased the firing rate of caudate Type I neurons and increased the firing rate, presumably via disinhibition (16), of globus pallidus (GP) Type II neurons. In the present study, extracellular single-unit recording techniques were used to demonstrate that systemic administration of the NMDA antagonist dizocilpine (MK801) reduced both the inhibition of caudate neurons by apomorphine as well as the apomorphine-induced excitation of GP neurons. In addition, the muscarinic antagonists atropine and scopolamine had effects similar to dizocilpine. Thus, both glutamate and acetylcholine appear to play a role in dopaminergic modulation of striatal and GP activity.

Acetylcholine↗
PubMed1996

Inhibition by noncompetitive NMDA receptor antagonists of apomorphine-induced climbing behavior in mice.

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is an important mediator of several forms of neural and behavioral plasticity. In the present study, we examined the potential role of NMDA receptors in the glutamatergic modulation of dopaminergic function at the postsynaptic dopamine receptor by determining the effects of NMDA antagonists on apomorphine-induced climbing behavior in mice. The noncompetitive NMDA receptor antagonists, MK-801, ketamine, dextrorphan, and dextromethorphan attenuated the apomorphine-induced climbing behavior at does well below those that produce untoward side effects. These results suggest that the NMDA receptors play important roles in the glutamatergic modulation of dopaminergic function at the postsynaptic dopamine receptors that mediate the apomorphine-induced climbing behavior in mice.

Animals↗
PubMed1982

Non-opiate beta-endorphin fragments and dopamine--III. gamma-Type endorphins and various neuroleptics counteract the hypoactivity elicited by injection of apomorphine into the nucleus accumbens.

The hypoactivity in rats induced by small doses of apomorphine, injected bilaterally into the nucleus accumbens area of the brain, could be antagonized by pretreatment with the neuroleptic-like neuropeptide des-enkephalin-gamma-endorphin (DE gamma E, beta-endorphin 6-17) as well as with the neuroleptic drugs haloperidol, sulpiride and clozapine injected into the accumbens. Dose-response studies revealed that a dose of 100 pg DE gamma E completely inhibited the apomorphine-induced hypomotility. The influence of DE gamma E appeared to be specific for gamma-type endorphins, since alpha-type endorphins were inactive in this respect. Treatment with DE gamma E injected into the accumbens for 4 days resulted in an enhancement of apomorphine-induced hypoactivity. It is concluded that gamma-type endorphins may control the activity of dopaminergic transmission in the nucleus accumbens, a suggestion which may be of significance for the purported neuroleptic-like and antipsychotic action of gamma-type endorphins.

Animals↗
PubMed1983

The influence of early postnatal treatment with haloperidol on the effects induced by small and large doses of apomorphine on locomotion of adult rats.

Chronic administration of haloperidol (0.5 mg/kg, s.c.) during early postnatal life did not modify the effects produced by a small dose of apomorphine (0.02 mg/kg, s.c.) on the locomotor activity of adult rats; conversely, the reduction of locomotion induced by a large dose of apomorphine (1 mg/kg, s.c.) was much more kared in haloperidol-pretreated rat than in saline-pretreated ones. The differential ontogeny of dopamine auto- and postsynaptic receptors could be partly responsible for the different influence of postnatal treatment with haloperidol on the responsiveness of the adult to small and large doses of apomorphine.

Animals↗
PubMed1983

Effects of apomorphine and methamphetamine on a quickly-learned conditioned-suppression response in rats.

Rats exhibited a marked suppression of motor activity when placed in the same chamber where they had been given electric shocks. Administration of apomorphine-HCl (0.1, 0.5 and 1.0 mg/kg, i.p.) attenuated the conditioned suppression, dose-dependently, but did not facilitate motor activity of control (i.e. non-shocked) rats. Methamphetamine-HCl (0.1, 0.5 and 1 mg/kg, i.p.) increased motor activity of both the shocked and non-shocked rats, in a dose-related manner. Haloperidol (0.3 and 1 mg/kg, i.p.), but not chlorpromazine-HCl (5 mg/kg, i.p.), enhanced the conditioned-suppression response. Atropine-sulfate (5 and 10 mg/kg, i.p.), p-chlorophenylalanine (300 mg/kg, i.p.) and alpha-methyl-p-tyrosine (100 mg/kg, i.p.) were slightly effective in reducing the conditioned-suppression response. Apomorphine- and methamphetamine-induced reduction of the conditioned-suppression response was inhibited by pretreatment with haloperidol. When catecholamine-synthesizing processes in rats were inhibited by pretreatment with alpha-methyl-p-tyrosine, or alpha-adrenergic receptor sites were blocked by pretreatment with phenoxybenzamine, the effect of methamphetamine, but not that of apomorphine, was reduced. Therefore, enhancement of dopaminergic neurotransmission may be responsible for attenuation of the conditioned-suppression response.

Animals↗
PubMed1984

The effects of yohimbine and neuroleptics on apomorphine-induced pecking behaviour in the pigeon.

The effects of yohimbine and some neuroleptics were investigated on pecking behaviour, induced by apomorphine. The total pecking counts, recorded for 18 min, elicited by a standard dose of apomorphine (1 mg/kg) were inhibited dose-dependently by yohimbine and the neuroleptics. Haloperidol was found to be the most potent, trifluoperazine, yohimbine, chlorpromazine and the atypical neuroleptics were less effective in decreasing order. Chronic treatment with yohimbine (2.5 mg/kg per day for 20 days) caused an increase in pecking behaviour. These results suggest that apomorphine-induced pecking behaviour in the pigeon could be used as a reliable method for screening neuroleptic drugs and the antidopaminergic activity of yohimbine is verified in this model.

Animals↗
PubMed1984

Behavioral and biochemical evidence of apomorphine-induced supersensitivity of the striatal dopamine receptors.

The effect of repeated administration of apomorphine was studied behaviorally and biochemically in rats bearing either a unilateral lesion of the substantia nigra with 6-OHDA or an electrolytic lesion of the entopeduncular nucleus. Rats with the nigral lesion displayed a progressive increase in contralateral circling rate. In animals with the entopeduncular lesion, the ipsiversive circling response was unchanged after the eight injection of apomorphine. [3H] Spiroperidol binding to striatal membranes did not appear modified by the apomorphine treatment on the intact side. It was however increased on the side of the 6-OHDA lesion. We propose that a denervated striatum responds to repeated stimulation by dopamine agonists with a paradoxical increase in sensitivity. This may explain in part the appearance of dyskinesia in treated parkinsonian patients.

Animals↗
PubMed1985

Differential effects of thioridazine, clozapine and metoclopramide on the induction of adrenomedullary enzymes by apomorphine.

The induction of two adrenomedullary enzymes, ornithine decarboxylase and tyrosine hydroxylase, by apomorphine was studied in rats receiving dopamine antagonists known to by specific in their site of action. Metoclopramide, a drug that acts predominantly on the A9 dopamine system, was effective in blocking the induction of the two enzymes by apomorphine. Thioridazine and clozapine, two antipsychotic drugs that act preferentially on the A10 dopamine systems, did not impair this induction and possibly potentiated it. The results suggest that the site of action of apomorphine responsible for the induction of adrenomedullary ornithine decarboxylase and tyrosine hydroxylase is located in the striatum.

Adrenal Medulla↗
PubMed1986

Influence of SCH 23390, a DA1-receptor antagonist, on the behavioural responsiveness to small and large doses of apomorphine in rats.

SCH 23390 (SCH), a DA1-receptor antagonist, did not influence the decrease in locomotor activity elicited by a dose of apomorphine (20 micrograms/kg) believed to stimulate DA autoreceptors in rats. Conversely, SCH antagonized the effects on locomotion and the stereotyped behaviour elicited by a dose of apomorphine (1 mg/kg) which stimulates postsynaptic DA receptors. These results showing that the behavioural effects produced by small and large doses of apomorphine are differently affected by SCH, further confirm that DA autoreceptors can be pharmacologically distinguished from postsynaptic DA receptors.

Animals↗
PubMed1988

Independent GABAergic and cholinergic modulation of apomorphine-induced stereotyped rearing in the rat.

The injection of GABA into the caudate nucleus inhibited the stereotyped rearing induced by apomorphine in a dose-related manner. Muscimol, a potent GABAergic agonist shared this effect. The inhibitory effect of GABA was easily counteracted by bicuculline but not by pretreatment with atropine. Injection of carbachol into the caudate nucleus inhibited the stereotyped rearing induced by systemically-applied apomorphine in a dose-related manner. This inhibitory effect was easily abolished by atropine but not bicuculline. Thus, the stereotyped rearing induced by apomorphine, an effect due to an increased excitatory state of the dopaminergic system in the caudate nucleus, could be modified (inhibited) by augmentation of either the GABAergic or of the cholinergic state excitation. The two modulatory systems did not appear to be interlinked; most probably, they influence the dopaminergic effect independently of one another.

Animals↗
PubMed1988

Striatal tissue transplants attenuate apomorphine-induced rotational behavior in rats with unilateral kainic acid lesions.

Four to six weeks following unilateral striatal kainic acid (KA) lesions, challenge with apomorphine (0.5-0.75 mg/kg s.c.) elicited rotational behavior. Gestational day 17-19 rat fetal striatal tissue was implanted into the lesioned striatum, and rats were rechallenged with apomorphine 10 weeks post-transplant. There was a significant reduction in the maximal rate of rotations and an alteration in the topography of locomotor activity in response to apomorphine. These data indicate that the transplanted material may possess similar pharmacological properties as the original host tissue and is capable of functionally repairing damage to a complex neurochemical system.

Animals↗
PubMed1986

Inhibition of protein kinase activity by apomorphine.

The effect of apomorphine (1-20 microM) on protein kinase activity was studied in extracts from rat peritoneal mast cells and brain tissue. Apomorphine inhibited the cyclic AMP-dependent and the calcium-plus phosphatidylserine-dependent protein kinase activity with an IC50 between 1 and 6 microM, depending on the tissue and on the protein kinase involved. This effect might explain previous results on the apomorphine-induced inhibition of histamine release in rat peritoneal mast cells.

Animals↗