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 289 records · Page 16Linked to original sources
PubMedDate not supplied

Psychooncology and cancer progression-related alterations of pleasure-associated neurochemical system: Abnormal neuroendocrine response to apomorphine in advanced cancer patients.

OBJECTIVES: The clinical approach of the Psychooncology is generally limited to the investigation of the only psychological status of cancer patients, without taking into consideration the well demonstrated cancer progression-related psychoneuroendocrine alterations, namely consisting of a progressive decline in the pineal endocrine function and an anomalous activity of brain opioid system. The endocrine response to apomorphine, a dopaminergic agent, has been proven to reflect the dopaminergic sensitivity, which would be involved at least in part in pleasure-related neurochemical mechanisms. The present study was performed to analyze the endocrine response to apomorphine in metastatic cancer patients, as a preliminary approach to the investigation of pleasure-related neuroendocrine mechanisms in human neoplasms. MATERIALS & METHODS: The study included 10 metastatic cancer male patients and 6 male volunteers as a control group. Apomorphine was given orally at 0.01 mg/kg body weight in the morning, and venous blood samples were collected before, and at 20, 60 and 120 minutes after apomorphine administration. The endocrine analysis consisted of the measurement of serum levels of GH, PRL and cortisol. RESULTS: All cancer patients presented alterations involving one or more endocrine responses to apomorphine. GH and cortisol mean levels after apomorphine were significantly higher in controls than in cancer patients, whereas no substantial difference occurred in those of PRL. CONCLUSIONS: This preliminary study, by showing an altered endocrine response to apomorphine in metastatic cancer patients, would suggest that cancer progression may be associated with an altered dopaminergic sensitivity. Because of the involvement of the dopaminergic system in pleasure-related neurochemical mechanisms, this finding would demonstrated that the decline in the perception of pleasure with cancer progression may depend not only on psychological factors, but also, at least in part, on psychochemical alterations occurring during the clinical course of the neoplastic disease.

Adult↗
PubMed1992

Behavioural responses to amphetamine and apomorphine in pigs.

The effects of different doses of amphetamine (0-1.5 mg/kg) and apomorphine (0-1.0 mg/kg) on behaviour of pigs were compared. Amphetamine induced an increase in levels of nosing and rooting and of locomotion. These increases were, however, related to increased levels of standing. At higher doses (1.0-1.5 mg/kg), amphetamine specifically induced a rigid standing posture with jerking head and limb movements. Apomorphine at 0.1-1.0 mg/kg increased locomotion. In contrast to amphetamine, this effect was specific as it was not explained by increased levels of standing. At 1.0 mg/kg, apomorphine specifically induced "locomotion while the pigs maintained snout contact with the floor or trough." In addition, at this dose it induced drinking in one test, while licking in another. These differences may in part be due to differences in the test environment. Apomorphine exerted a strong conditioning effect, as indicated by the lack of behavioural variability in the postinjection period. This effect may explain the large interindividual variation in apomorphine response. Amphetamine and apomorphine elicit different behavioural syndromes in pigs, suggesting that they act on different neural systems. In addition, neither amphetamine nor apomorphine elicited behaviour that closely resembles environmentally induced stereotypies.

Amphetamine↗
PubMed1990

Functional interaction between serotonin-S2 and dopamine-D2 neurotransmission as revealed by selective antagonism of hyper-reactivity to tryptamine and apomorphine.

The functional significance of the interaction between serotonergic and dopaminergic neurotransmission is still uncertain. To document this interaction further, specific behavioral responses of rats to tryptamine and apomorphine were studied. The sequential injection of these agonists, at time intervals with minimal direct behavioral interference, was used to observe response changes with respect to a single challenge. The antagonists haloperidol, ritanserin and risperidone, with known actions on serotonin-S2 (5-HT2) and dopamine-D2 (D2) receptors were used to evaluate effective antagonism of single and sequential challenges. When tryptamine was preceded by an apomorphine challenge the effective doses of the 5-HT2 antagonists ritanserin and risperidone for 50% inhibition of the seizures increased by a factor of 2.5. The dose-response curve of haloperidol remained virtually unchanged, apparently because of the potent dopamine-D2 antagonism associated with these doses which may block the potentiating effect of apomorphine. When apomorphine was preceded by a tryptamine challenge, the total agitation score of the control animals increased by 59% on the average. Haloperidol was equally effective against the enhanced as against the unenhanced apomorphine response. Ritanserin reduced agitation only by the part corresponding to the tryptamine enhancement. Risperidone's activity against the enhanced agitation started at very low doses and was complete at a dose still about 2.5 times lower than that required against the single apomorphine challenge. Mutual enhancement of tryptamine and apomorphine appears to occur even at a time when the behavioral effects of the first agonist are no longer manifest. The enhanced agitation remains largely dopamine-D2-specific and the enhanced seizures serotonin 5-HT2-specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

SCH23390 effects on apomorphine-induced responses of nigral dopaminergic neurons.

SCH23390 is a dopamine antagonist which has a high affinity for D1-like dopaminergic receptors. Receptor binding studies demonstrated significant levels of specific SCH23390 binding within nigral tissue. Therefore, electrophysiological experiments were conducted to determine if this antagonist influenced apomorphine-induced suppressions of unit firing recorded from dopaminergic cells of the substantia nigra zona compacta. Results presented in this report indicate that the autoreceptors located on dendrites and cell bodies of dopamine-containing neurons are not directly acted upon by SCH23390. This conclusion is drawn because: doses of SCH23390 known to block behaviors caused by dopamine agonists were ineffective in blocking rate reductions produced by apomorphine and pretreatment with 0.1 mg/kg of SCH23390 did not change the apomorphine dose-response curve for inhibition of dopaminergic neurons. Consistent with this finding, microinjections of SCH23390 into the zona compacta did not alter apomorphine-induced behaviors which are known to be blocked by haloperidol (a D2-like antagonist) intranigral injections. However, when only the larger apomorphine doses (64 and 128 micrograms/kg i.v.) are considered, SCH23390 pretreatment did attenuate the maximum response to apomorphine in some nigral cells. Because larger apomorphine concentrations alter striatal activity, such results may be reflective of alterations in a subpopulation of nigral neurons which are postsynaptic to neurons containing D1-like receptors and located elsewhere in the brain (e.g., in striatum). Collectively, these results agree with previous studies which suggest that dopamine receptors located on dopamine-containing neurons of the substantia nigra zona compacta are likely not of the D1-type.

Analysis of Variance↗
PubMed1987

Involvement of membrane sulfhydryl groups in apomorphine-induced inhibition of neutrophil migration.

Apomorphine inhibits fMet-Leu-Phe stimulated migration of rabbit neutrophils, in the absence of albumin, in the concentration range of 1-20 microM. In the presence of albumin inhibition by apomorphine occurs at higher concentrations. Casein-stimulated migration, and non-stimulated migration are equally inhibited by apomorphine. The presence or absence of extracellular Ca2+ has no effect on the degree of inhibition by apomorphine. The ability of albumin to interfere with apomorphine inhibition of migration is diminished after treatment of albumin with the sulfhydryl reagent N-ethylmaleimide. Sulfhydryl compounds, such as glutathione and dithiothreitol, strongly interfere with apomorphine inhibition. The results suggest that the inhibiting effect of apomorphine is due to a reaction with sulfhydryl groups, the intactness of which is required for neutrophil migration, and which are probably located on the plasma membrane.

Albumins↗
PubMedDate not supplied

Implications of changes in apomorphine-induced hypothermia after prenatal exposure to phenobarbital.

Pregnant mice were exposed to phenobarbital (PhB) on gestation days 9 to 18 (3 gm/kg milled food). Their offspring, who were exposed to the drug transplacentally (B offspring), were tested at an age of 50 days for apomorphine- (0.5, 1.0 and 2.0 mg/kg) induced hypothermia. At doses of 1.0 and 2.0 mg/kg, B offspring had less hypothermic response to apomorphine than controls (p less than 0.01); the effect was similar in both sexes. In order to acquire further understanding of the alterations in apomorphine hypothermia, mainly in relation to dopamine (DA) receptors, adult intact mice were exposed to haloperidol for 4 weeks (25 mg/kg milled food) in order to increase their DA receptor number, and their hypothermic response to apomorphine was tested 4 days post withdrawal. The treated animals had an increased DA receptor number, as was attested by a 23% increase in 3H-spiroperidol binding (P less than 0.01) and a 77% increase in apomorphine-induced climbing. However, their apomorphine-induced hypothermia did not differ from control. Therefore, there is no evidence as yet that alterations in apomorphine-induced hypothermia after prenatal exposure to PhB indicates changes in DA receptors, and the implications of this phenomenon still remain an open question.

Animals↗
PubMed1982

Differential liabilities of haloperidol and thioridazine for inducing apomorphine hypersensitivity.

In an animal model of tardive dyskinesia, sensitivity to apomorphine-induced stereotyped behavior reflects increased dopamine receptor activity induced by chronic neuroleptic treatment. Four groups of Sprague-Dawley rats received haloperidol (H) 0.5 mg/kg, haloperidol 0.5 mg/kg + benztropine 2.0 mg/kg (H + B), thioridazine (T) 25 mg/kg, or saline (S) ip daily for 18 days, were withdrawn for 21 days, and then received another 10 days of drug. Drug-induced catalepsy was measured daily during the second phase of drug treatment. Sensitivity to apomorphine 0.125 mg/kg and 0.250 mg/kg was assessed during the first and second weeks of withdrawal from each phase of drug treatment. Catalepsy scores for H, H + B, and T groups showed an unexpected progressive increase over treatment days. Following withdrawal from the first drug phase, only H and H + B rats showed enhanced apomorphine stereotypy. H rats were hypersensitive for both weeks of testing while H + B rats were only hypersensitive for the first week. All rats showed changes in apomorphine sensitivity after withdrawal from the second drug phase. H and H + B rats showed significant enhancement of stereotypy at both apomorphine dose levels and at both weeks of testing. T rats showed a significant enhancement but only at the higher apomorphine dose level and only during the first withdrawal week. S rats had a significant enhancement of apomorphine-induced stereotypy during the second withdrawal week. We conclude that H, H + B, and T have differential liability for inducing dopamine receptor hypersensitivity, with haloperidol being most effective and thioridazine being least effective.

Animals↗
PubMedDate not supplied

[Sensitization of male rats to aggressive behavior by apomorphine].

In experiments on male Wistar rats it was established that following a 10 days treatment with low doses (0.1 mg/kg) of apomorphine, tolerance developed to its sedative effects, while aggression to foot-shocks was markedly enhanced. Administration of apomorphine (0.5 mg/kg) and amphetamine (2.5 mg/kg) after chronic low dose apomorphine treatment revealed an enhancement of their effects - stereotypy and aggressiveness was observed. Nalorphine, blockader of opiate receptors, after sensibilization of male rats with apomorphine also caused an increase of aggression to foot-shocks. Nalorphine antagonized, as low doses of apomorphine did, antiaggressive action of morphine. It is suggested that long-lasting treatment with apomorphine enhances the sensitivity of dopamine receptors to agonists, and of opiate receptors to antagonists. These changes on synaptic level are possibly involved in the phenomenon of apomorphine hyperaggressiveness.

Aggression↗
PubMedDate not supplied

Pharmacodynamics of levodopa coadministered with apomorphine in parkinsonian patients with end-of-dose motor fluctuations.

The modification of the pharmacodynamic response to a single oral dose of levodopa/benserazide by the coadministration of the dopamine agonist apomorphine was investigated in parkinsonian patients with end-of-dose motor fluctuations. The relation between levodopa plasma concentrations and motor response was examined in a double-blind, randomized, crossover design in 10 patients with idiopathic Parkinson's disease with end-of-dose motor fluctuations. Oral single-dose challenges with 100 mg of levodopa/25 mg of benserazide were carried out twice in each patient, under coadministration with apomorphine (1 mg/h) or 0.9% saline (placebo) subcutaneously. The sum scores (sigma score) of the Columbia University Rating Scale (CURS) were used as effect parameters for pharmacodynamic assessment. A sigmoidal Emax model was fitted to the data using a semiparametric pharmacokinetic-pharmacodynamic approach. Levodopa pharmacokinetics were not significantly modified by the coadministration of apomorphine. The area under the curve was 1599 +/- 615 ng.ml-1 h. (levodopa + saline) and 1821 +/- 625 ng.ml-1.h (levodopa + apomorphine). Cmax was 1094 +/- 476 ng.ml-1 (levodopa + saline) and 1129 +/- 435 ng.ml-1 (levodopa + apomorphine). Under both experimental regimens, the maximum clinical response to levodopa (Emax) yielded a decrease in the CURS sigma rating of about 20 score points. Estimates of the EC50 of levodopa decreased significantly from 430 +/- 163 ng.ml-1 (levodopa + saline) to 315 +/- 123 ng+ml-1 (levodopa + apomorphine) (95% confidence interval [CI] 0.51 -0.98, point estimator 0.75). The mean duration of the motor response rose from 1.9 +/- 0.5 h (levodopa + saline) to 3.0 +/- 0.9 h (levodopa + apomorphine (95% CI 1.23 to 2.06, point estimator 1.60). Thus, a reduction of the threshold levels for levodopa (EC50) was accompanied by approximately 50% gain in on-phase duration, but not in an increased magnitude of the motor response (Emax).

Adult↗
PubMed1998

Effects of bilateral ablation or 6-OHDA lesion of the frontal cortex upon the behaviors induced by apomorphine and amphetamine in adult cats.

The main aim of this study was to compare the effects of bilateral 6-OHDA lesion of the prefrontal, frontal and media cerebral cortex, with those of suction ablation of the same areas, upon apomorphine and amphetamine evoked behaviors. Twenty five cats were distributed in four groups: 1) 8 cats received bilateral, injection of 6-OHDA (32 micrograms per hemisphere), and the behaviors elicited by separate injection of apomorphine (2.0 mg/kg s.c.) and amphetamine (2.5 mg/kg s.c.) before and after the lesion were compared; 2) 3 cats received a unilateral injection of 6-OHDA into the cited areas and dopamine concentration on the lesioned site and the contralateral non-lesioned side were compared; 3) 8 cats had bilateral suction ablation of the cited cortical areas and the results of apomorphine and amphetamine evoked behaviors before and after ablation were compared, and 4) the effects of solvent injections and sham operations were studied in 6 additional cats. 6-OHDA lesion had scanty effects on the behaviors evoked by apomorphine and amphetamine. Only two (fear like behavior and lack of food motivation) out of 9 behaviors elicited by apomorphine were modified, while two of five behaviors elicited by amphetamine (immobility and food motivation) showed a change. On the other hand, the ablation procedure had a much wider effect on the behaviors elicited by the dopaminergic agonist drugs. All 5 behaviors evoked by amphetamine were modified, while only 4 of nine behaviors induced by apomorphine did change. These results show the importance of the interplay between dopamine and the target tissue that receive the dopaminergic fibers in the production of the behaviors evoked by parenteral injection of apomorphine and amphetamine.

Age Factors↗
PubMed1998

An integrated pharmacokinetic-pharmacodynamic approach to optimization of R-apomorphine delivery in Parkinson's disease.

R-apomorphine is a mixed dopamine D(1)/D(2) receptor agonist which is potentially useful in the management of Parkinson's disease. The delivery of R-apomorphine is complicated however by a number of pharmacokinetic and pharmacodynamic factors. This review describes the development of a transdermal iontophoretic delivery system for R-apomorphine on the basis of integrated pharmacokinetic-pharmacodynamic (PK/PD) investigations in patients with idiopathic Parkinson's disease. The pharmacokinetics and metabolic pathways of R-apomorphine were determined following intravenous infusion of 30 µg kg(-1) in 15 min in 10 patients. A stepwise infusion protocol was used to determine the therapeutic window. A wide interindividual variability in both pharmacokinetics and pharmacodynamics and a narrow therapeutic concentration range were observed. This shows the need for individualized and carefully controlled delivery of R-apomorphine in Parkinson's disease. Transdermal iontophoretic transport was studied both in vitro in human stratum corneum and dermatomed full skin and in vivo in patients with Parkinson's disease. These studies showed that the delivery of R-apomorphine by transdermal iontophoresis is feasible and furthermore that the rate of delivery can be carefully controlled by variation of the current density. It is concluded that the delivery of R-apomorphine by transdermal iontophoresis may be an attractive tool in future clinical pharmacological investigations in patients with Parkinson's disease aiming at characterization of the influence of chronic treatment and disease progression on the pharmacokinetics and pharmacodynamics. Ultimately these studies may result in a system which is suitable for clinical application.

Journal Article↗
PubMed1994

Transient hypersensitivity to apomorphine-induced gnawing after termination of acute effects of a single high dose of cocaine.

Physical dependence on cocaine has not been fully characterized or definitively identified. Since behavioral changes are typically not observed after cocaine withdrawal in animal studies, we sought to amplify or reveal any such changes in behavior by administration of the dopamine agonist apomorphine. C57BL/6J mice were tested for behavioral effects (climbing, gnawing, and locomotor activity) of apomorphine at various times after acute administration of cocaine. When tested at a time when most of the administered cocaine had disappeared from brain and when behavioral effects of cocaine had dissipated, at 2 and 4h post cocaine administration, effects of apomorphine on gnawing were increased 4-fold. This dopaminergic hypersensitivity was induced by acute treatment with doses of 15mg/kg cocaine and higher. Effects of apomorphine were not enhanced at later time periods (6 to 24h after cocaine), indicating a rapid waning of the dopaminergic hypersensitivity. Hypersensitivity to apomorphine was not further augmented by 8 days of daily cocaine injections. Cocaine did not influence climbing and hypomotility induced by apomorphine 4h after its injection, demonstrating selectivity in the behavioral expression of the dopaminergic hypersensitivity. Further, cocaine did not induce sensitization to its own effects indicating that the hypersensitivity to apomorphine was not due to a typical sensitization phenomenon. The results of these experiments demonstrate a short-lived dopaminergic supersensitivity after termination of the acute effects of a single high dose of cocaine, the implications of which remain to be discovered.

Journal Article↗
PubMed1992

Apomorphine test for dopaminergic responsiveness in patients with previously untreated Parkinson's disease.

We prospectively examined the predictive value of the apomorphine test for the therapeutic efficacy of sustained oral levodopa treatment in 62 patients with de novo Parkinson syndrome (no additional neurological deficit) who had not previously been treated with dopaminergic medication. Patients received 2 to 5 mg of apomorphine hydrochloride subcutaneously and a subsequent trial of oral levodopa of at least 3 months' duration. In three patients, response to apomorphine could not be evaluated owing to side effects experienced during the test. In the remaining 59 patients, the best predictor of response to oral levodopa was the apomorphine-induced relative decrease in the scores on the motor examination part of the Unified Parkinson Disease Rating Scale (UPDRS). At a cutoff value of 20% improvement in UPDRS scores, the test predicted the response to levodopa correctly in 50 patients (85%). The sensitivity of the test was 90%, specificity 88%. The positive predictive value was 95%. However, seven of 19 apomorphine test-negative patients experienced a good (n = 4) or partial (n = 3) improvement with levodopa therapy. Thus, the negative predictive value was only 63%. We conclude that response to apomorphine has a high predictive value for response to sustained oral levodopa treatment in most previously untreated patients, but a negative test should not preclude an adequate trial of oral levodopa.

Adult↗
PubMed2001

Increased growth hormone response to apomorphine in Parkinson disease compared with multiple system atrophy.

BACKGROUND: Parkinson disease (PD) is often difficult to distinguish from parkinsonian syndromes of other causes in early stages of the disease. In search of a suitable endocrinologic challenge test, we investigated dopaminergic sensitivity in patients with de novo parkinsonian syndromes. OBJECTIVE: We measured the growth hormone (GH) response to a subthreshold dose of the dopamine 1-dopamine 2 receptor agonist apomorphine hydrochloride to differentiate parkinsonian syndromes from PD. PATIENTS AND METHODS: Seventeen patients with a clinical diagnosis of PD, 16 patients with a clinical diagnosis of multiple system atrophy, and 11 healthy controls. The GH response to a subthreshold dosage of apomorphine and to somatorelin (GH-releasing factor) was tested in a randomized order; on the third day the protocol was repeated with a clinically effective dose of apomorphine. RESULTS: The GH response to the low dose of apomorphine was significantly increased in patients with PD when compared with patients with multiple system atrophy or the control subjects (multivariate analyses of covariance; univariate F test, all P<.05). In contrast, there were no significant group differences with use of the higher dose of apomorphine or in the somatorelin-induced GH release. CONCLUSIONS: The GH response to a subthreshold dose of apomorphine appears to be a useful tool to identify patients with PD vs multiple system atrophy. The enhanced GH response to a subthreshold dopaminergic stimulus may reflect a hypersensitivity of the extrastriatal dopamine receptors in PD.

Adrenocorticotropic Hormone↗
PubMed1980

Behavioural effects of chronic treatment with apomorphine in combination with neuroleptic drugs.

Groups of male Wistar rats were injected with either apomorphine alone twice daily for one week or with apomorphine in combination with chlorpromazine or thioridazine. The neuroleptics were administered once daily so that it was possible to assess their duration of effect on the apomorphine responses. Other groups were injected with saline (controls) chlorpromazine or thioridazine. The nature and time of onset and duration of the stereotyped response following apomorphine injection was determined twice daily. In addition, the behaviour of the rats on the hole board apparatus was also assessed after seven days of drug treatment. Apomorphine was found to induce either a "sniffing/burrowing" or a "fighting" stereotypy. Chlorpromazine increased the latency and reduced the duration of both types of stereotypy. In contrast thioridazine only increased the latency and reduced the duration of response the "fighting" group. On the hole board apparatus, both neuroleptics reduced the ambulation and rearing scores of the "fighting groups alone. It is suggested that the different types of stereotypy induced by chronic apomorphine administration, and their sensitivity to the two neuroleptics, are mediated by different types of dopamine receptors.

Aggression↗
PubMed1998

A double-blind, placebo-controlled study of intranasal apomorphine spray as a rescue agent for off-states in Parkinson's disease.

Nine patients with advanced levodopa-responsive Parkinson's disease were enrolled in a double-blind, placebo-controlled crossover trial of intranasal apomorphine as rescue therapy for parkinsonian off-states. Patients were assigned in random order to each of four possible combinations of apomorphine, trimethobenzamide antiemetic, and their matched placebos and received detailed in-office motor scoring during each of the four study periods. Patients also completed diaries describing the effectiveness of the nasal spray for reversing off-states. A statistically significant reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score was seen following active apomorphine during in-office evaluation visits but not following placebo nasal spray. Patient diaries revealed that active apomorphine had a latency to onset of 11 minutes and a duration of 50 minutes. Significant nausea from apomorphine spray was seen in only one patient whereas nasal irritation was disabling in three and mild in two. We conclude that intranasal apomorphine is an effective rescue agent for parkinsonian off-states although nasal irritation is a limiting factor.

Administration, Intranasal↗
PubMed1991

Partial dopamine depletions result in an enhanced sensitivity of residual dopamine neurons to apomorphine.

Extracellular recordings from identified dopamine neurons were used to assess the effect of 6-hydroxydopamine-induced partial lesions of the nigrostriatal dopamine system on the sensitivity of the residual dopamine neurons to the dopamine agonist apomorphine. This was done by testing the response of identified nigral dopamine neurons in control and lesioned rats to systemic apomorphine administration at two time points: 1) 6-10 days post-lesion, when the loss of dopamine cells is nearly complete, and 2) 4-8 weeks post-lesion, which should be sufficient time for changes in dopamine receptor density to occur. As reported previously, dopamine neurons in control rats were inhibited by systemic administration of apomorphine, with their sensitivity being inversely related to their initial firing rate. The sensitivity of the residual dopamine neurons to apomorphine was unaltered in rats tested 6-10 days after depletions of at least 60% of striatal dopamine. However, by 4-8 weeks post-lesion, there was a significant increase in the sensitivity to apomorphine; furthermore, sensitivity was no longer related to baseline firing rate, but instead was uniformly high in all dopamine neurons tested at this time. This enhanced sensitivity was not altered by hemisection of the striatonigral projection, suggesting that the increased sensitivity to apomorphine was most likely a result of a time-dependent up-regulation of somatodendritic autoreceptors on the residual dopamine neurons.

Animals↗
PubMed1993

Neurochemical correlates of behavioral sensitization following repeated apomorphine treatment: assessment of the role of D1 dopamine receptor stimulation.

Previous research has revealed a role of repeated D1 dopamine receptor stimulation in the development of behavioral sensitization to the D1/D2 agonist apomorphine. The present experiments assessed the role of repeated D1 receptor stimulation in neurochemical changes accompanying locomotor sensitization to apomorphine. To assess direct effects of D1 stimulation on dopamine synthesis, rats were injected with the D1 agonist SKF 38393 (8 mg/kg), followed by an injection with the 3,4-dihydroxyphenylalanine (DOPA) decarboxylase inhibitor, NSD-1015. DOPA accumulation, assessed in striatal, nucleus accumbens-olfactory tubercle (NAOT), and ventral mesencephalon (VM) tissue samples, was not affected by acute SKF 38393. In the second experiment, rats were treated with 10 daily injections of vehicle, apomorphine (5 mg/kg) or the D1 agonist SKF 38393 (8 or 16 mg/kg). Daily measures of locomotor activity demonstrated a progressive increase in the apomorphine-treated rats, but not the SKF 38393-treated rats, across the 10 days. On day 11, all rats were injected with NSD-1015 for measurement of DOPA accumulation. Dopamine synthesis was enhanced in the striatum after repeated apomorphine treatment. In contrast, repeated SKF 38393 treatment resulted in either a small decrease or no change in DOPA accumulation in the different brain regions (striatum, NAOT, VM). In the third experiment, tissue levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and [3H]SCH 23390 binding to D1 receptors were measured in rats treated with 10 daily injections of vehicle, apomorphine (5 mg/kg), or SKF 38393 (16 mg/kg). In the striatum and NAOT, none of the repeated drug treatments had an effect on DOPAC or dopamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

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