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PubMed1991

The 5-HT3 receptor antagonists LY 277359 and granisetron potentiate the suppressant action of apomorphine on the basal firing rate of ventral tegmental dopamine cells.

In this study, we examined the effect of the 5-HT3 receptor antagonists LY 277359 and granisetron on the suppressant action of the dopamine receptor agonist (+/-)-apomorphine on spontaneously active dopamine cells in the substantia nigra pars compacta (SNC or A9) and ventral tegmentum area (VTA or A10) in the rat. This was accomplished using the standard extracellular single unit recording techniques. The i.v. administration of (+/-)-apomorphine (1-64 micrograms/kg) produced a dose-dependent suppression of the basal firing rate of spontaneously active A9 and A10 dopamine cells. The i.v. administration of LY 277359 at 0.01 and 0.1 mg/kg, but not 1 or 10 mg/kg, potentiated the suppressant action of (+/-)-apomorphine on A10 dopamine cell firing. In contrast, (+/-)-apomorphine's suppressant action on the firing rate of A10 dopamine neurons was potentiated by all doses of granisetron except the 10 mg/kg dose. The suppressant action of (+/-)-apomorphine in control and pretreated rats was reversed by the i.v. administration of haloperidol (0.05-0.1 mg/kg). In contrast, the suppression action of (+/-)-apomorphine on the firing rate of A9 dopamine cells was not altered by any dose of LY 277359 or granisetron. Overall, our results suggest that LY 277359 and granisetron selectively potentiate the response of A10 dopamine cells to (+/-)-apomorphine.

Animals↗
PubMed1995

Effects of GBR 12909 on locomotor activity and dopamine turnover in mice: comparison with apomorphine.

The effects of GBR 12909 1-[2-[bis(4-fluorophenyl)methoxy]-ethyl]-4- [3-phenylpropyl]piperazine, a very potent and selective dopamine uptake inhibitor, and apomorphine, a dopamine receptor agonist, alone and in combination were investigated on locomotor activity and dopamine turnover in discrete brain regions of mice. The levels of dopamine and its metabolites were examined 40 min after the administration of GBR 12909 and/or apomorphine, when the effects of the drugs on locomotor activity were approximately at a peak. GBR 12909 (10 mg/kg i.p.) reversed a low dose of apomorphine (0.05 mg/kg s.c.)-induced suppression in locomotor activity and significantly increased this activity. Despite the dramatic change in the behavior, GBR 12909 did not influence the decrease in 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine ratio (which is one of the indications of transmitter turnover) induced by a low dose of apomorphine in the nucleus accumbens and striatum. In contrast, GBR 12909 did not enhance the high-dose apomorphine (2 mg/kg s.c.)-induced hyperlocomotion, and did not modify the larger decrease in dopamine turnover produced by the high dose of apomorphine in the frontal cortex, nucleus accumbens and striatum. This suggests that postsynaptic dopamine receptors may reach maximum stimulation at a high dose of apomorphine. These results indicate that a behavioral change induced via stimulation of postsynaptic dopamine receptors does not necessarily lead to an alteration in dopamine turnover.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Pharmacological characterization of apomorphine-induced hypothermia in the spontaneously hypertensive rat.

The dopamine agonist apomorphine was more potent in eliciting hypothermia in spontaneously hypertensive rats (SHRs) than in normotensive Wistar rats (NWRs), while normotensive Wistar-Kyoto rats (WKYs) were intermediate in response. Various drug interventions were attempted in an effort to explain the greater sensitivity of SHRs to apomorphine. Haloperidol produced abolition of apomorphine-induced hypothermia in SHRs but at greater doses than required for antagonism of the drug effect in WKYs and NWRs. Chronic hydralazine treatment that reduced the high blood pressure of SHRs failed to appreciably influence the magnitude of apomorphine-induced hypothermia, compared to the response in control SHRs that received no hydralazine. These findings suggested to us that the enhanced hypothermic effect of apomorphine in SHRs was entirely dopamine receptor-mediated and that it was also independent of the high blood pressure. We also found that chronic lithium treatment that had no influence upon apomorphine-induced hypothermia in WKYs and NWRs significantly reduced the drug effect in SHRs. Based on this finding, we suggest that the greater hypothermic effect induced by apomorphine in SHRs might be due to a supersensitivity of hypothermia-mediating dopamine receptors in the hypertensive strain.

Animals↗
PubMed1982

Effect of apomorphine, piribedil and haloperidol on adrenal ornithine decarboxylase activity of the rat.

The administration of the dopaminergic drugs, apomorphine and piribedil to rats resulted in an increase in the activity of ornithine decarboxylase of the adrenal medulla and cortex. Pretreatment of the rats with the dopamine-receptor antagonist haloperidol caused a partial blockade of the apomorphine-induced effect at 4 hr in both medulla and cortex. At 6 hr, however, haloperidol did not block the effect of apomorphine and produced an increase in ornithine decarboxylase activity of both structures when administered alone. Hypophysectomy abolished the cortical ornithine decarboxylase response to apomorphine and haloperidol and the medullary response to haloperidol. The results suggest that the response of cortical ornithine decarboxylase activity to apomorphine and haloperidol is entirely mediated by the hypophysis and that the effect of apomorphine and the antagonistic action of haloperidol towards apomorphine in regard to the induction of adrenal medullary ornithine decarboxylase must be taking place at some central site independent of the hypothalamic-hypophyseal system.

Adrenal Glands↗
PubMed1982

Effects of naloxone on d-amphetamine- and apomorphine-induced behavior.

The effects of acute naloxone administration on d-amphetamine- and apomorphine-induced behavior were studied. Naloxone, in doses of 0.3-10 mg/kg (s.c.), antagonized the increase in ambulation and rearing induced by 1 mg/kg of d-amphetamine. When the dose of d-amphetamine was increased to 3 mg/kg, naloxone (3 mg/kg) antagonized only the increase in rearing activity. No dose (0.3-10 mg/kg, s.c.) of naloxone significantly affected d-amphetamine- or apomorphine-induced stereotyped activity. Naloxone (3 mg/kg) significantly augmented the apomorphine (1 mg/kg, s.c.)-induced increase in ambulation but attenuated the apomorphine (0.3 mg/kg)-induced increase in rearing activity. Naloxone (3 mg/kg) or apomorphine (0.03 mg/kg) significantly decreased the ambulation and rearing induced by a novel environment. In combination and in these doses, naloxone and apomorphine produced an additive effect on these behaviors. The neurochemical mechanisms by which naloxone affects d-amphetamine- and apomorphine-induced behavior were investigated. Naloxone (10(-6) M) had no significant effect on [3H]spiroperidol binding in either the caudate nucleus or nucleus accumbens except for a modest inhibition (24%) of both the Km and Bmax in the accumbens microsomal fraction. Similarly, naloxone (10(-6) M) had no significant effect on [3H]dopamine(DA) uptake into either brain region nor did naloxone alter the d-amphetamine-inhibition of uptake. Using perfused tissue slices, naloxone (10(-6)-10(-5) M) significantly attenuated the increase in [3H]DA release induced by d-amphetamine (10(-5) M) in both brain regions. Naloxone (1 mg/kg) had no significant effect on DA or dihydroxyphenyl-acetic acid (DOPAC) levels or on the DA/DOPAC ratio in the caudate nucleus or nucleus accumbens. However, naloxone did reverse the marked increases in the DA-DOPAC ratio induced by d-amphetamine (1 mg/kg) in both brain regions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Non-opiate beta-endorphin fragments and dopamine--I. The neuroleptic-like gamma-endorphin fragments interfere with the behavioural effects elicited by small doses of apomorphine.

In rats, the beta-endorphin fragment, 6-17 (des-enkephalin-gamma-endorphin, DE gamma E), dose-dependently antagonized the reduction of the rate of locomotion and rearing induced by small doses of apomorphine. Structure-activity studies revealed that the active moiety of gamma-endorphin fragments with respect to counteracting apomorphine-induced behavioural changes resides in the fragment 6-17. The influence of DE gamma E appeared to be specific for dopamine systems mediating apomorphine-induced hypomotility, since DE gamma E hardly affected apomorphine-induced stereotypy and amphetamine-induced behavioural changes. These data suggest that DE gamma E acts as a dopamine antagonist selectively, on those dopamine receptor systems which are stimulated by small doses of apomorphine and which may be located presynaptically. In contrast to acute treatment, administration of DE gamma E for 4 days resulted in an enhancement of apomorphine-induced hypomotility. Thus, the receptor systems involved in these effects of apomorphine may become supersensitive upon (sub)chronic treatment with DE gamma E. The significance of the present findings are discussed in relation to the neuroleptic-like and antipsychotic action of gamma-type endorphins.

Animals↗
PubMed1984

Binding of [3H]apomorphine to an aporphine binding site as well as to dopamine sites in tissue from bovine caudate nucleus.

Binding of the tritiated dopamine (DA) agonists, apomorphine (APO) and a dihydroxyaminotetralin (ADTN) to a membrane preparation from the caudate nucleus of calf brain was compared. Binding of [3H]dihydroxyaminotetralin at small (nM) concentrations followed simple, monophasic inhibition (over 80% at less than 500 nM) by concentrations of apomorphine between 50 pM and 1 mM. Inhibition of the binding of [3H]apomorphine by dihydroxyaminotetralin was more complex, and included in component with a low (microM) affinity for dihydroxyaminotetralin accounting for approx. 20% of total binding. The kinetics of binding of the ligands to high-affinity sites were virtually identical (apparent Kd = 0.81 nM; Bmax = 211 fmol/mg protein) and could not be distinguished by curve-fitting techniques adapted to analysis by microcomputer. In contrast, the binding of [3H]apomorphine with a "blank" defined by excess (10 microM) dihydroxyaminotetralin could be resolved into the same high-affinity component and a lower-affinity site (Kd = 124 nM; Bmax = 5740 fmol/mg). The pharmacology of the lower-affinity binding of [3H]apomorphine was evaluated by coincubating with 0.5 microM dihydroxyaminotetralin to "mask" high-affinity sites, and was compared to high-affinity binding of [3H]apomorphine and [3H]dihydroxyaminotetralin. The high-affinity binding was stereoselective for DA receptor agonists and antagonists. The pharmacology of the lower-affinity site resembled no known DA receptor type and showed highest affinities for aporphines but was not stereoselective and reacted weakly and nonspecifically with dihydroxyaminotetralin, DA, other catecholamines and neuroleptics. Thus, [3H]apomorphine, under certain conditions, may detect an aporphine binding site of uncertain pharmacological significance, as well as high-affinity DA agonist (D-3) sites.

Animals↗
PubMed1984

Effect of age on behavioral responses and tissue levels of apomorphine in the rat.

Rats of several ages between 2 and 24 months were tested for stereotyped behavioral responses to R(-)apomorphine-HCl (APO), a potent and selective dopamine agonist. Between 2 and 24 months, the ED50 for apomorphine decreased 2.5-fold (0.14-0.06 mg/kg, i.p.), as assessed by a microcomputer-assisted technique. Not only were older rats more sensitive to apomorphine, but the duration of the behavioral effects increased with age and showed a greater change at doses which were greater than the ED50. When levels of apomorphine in brain were assayed by liquid chromatography and electrochemical detection, there was a progressive increase in peak levels of the agent in the tissue as well as a delay in its elimination from brain, with increasing age. Moreover, there was a highly significant correlation between increased behavioral effect and the level of apomorphine in brain with increasing age (r greater than 0.8). These results indicate that increased levels in brain or decreased elimination of apomorphine may be an important factor contributing to a marked increase in behavioral sensitivity to apomorphine with age in the rat.

Aging↗
PubMed1984

Episodic excitation and changes in aggressive behavior induced by apomorphine in rats subjected to REM sleep deprivation.

Behavioral changes induced by apomorphine in normal, pseudodeprived (control) and REM sleep-deprived AM-2/TOR inbred rats were investigated. Deprived rats exhibited aggressive behavior for nearly 30 min in the absence of administration of drug, this effect not being observed in normal or control rats. The administration of apomorphine (1, 2 and 5 mg/kg) 5 min before the test elicited short periods of aggressive behavior in normal and control rats, but decreased the total duration of aggressive behavior in deprived rats. However, the deprived rats exhibited a more intense aggressive behavior, since the frequency of real fighting events was enhanced. The administration of apomorphine to deprived rats elicited stereotyped behavior. Enhancement of stereotyped behavior by increasing the dose was correlated with a reduction in the duration of aggressive behavior. Apomorphine also induced short episodes of intense excitability, manifested by increased locomotor activity, jumping and vocalization. This behavioral response was termed "episodic excitation". Deprived rats were significantly more sensitive to apomorphine-induced episodic excitation than normal and control rats. The episodic excitation, stereotyped and aggressive behavior displayed by deprived rats, injected with apomorphine, alternated with time. The results demonstrate increased responsiveness to apomorphine after deprivation of REM sleep. The possible mechanism for such interaction is discussed.

Aggression↗
PubMed1990

The effect of chronic apomorphine treatment on the ultrastructure of the prolactin cells and on plasma prolactin levels in young and aged male Wistar rats.

Effects of two doses of apomorphine on the plasma prolactin (PRL) levels and on the ultrastructure of PRL cells in young and aged male Wistar rats were investigated. In young and aged control rats no significant differences were found between the plasma PRL levels. Immunocytochemical staining with anti-r-PRL revealed significant differences between young and aged control rats; in young rats the number of PRL cells with polymorphic granules exceeded the number of cells with round granules, whereas in aged rats almost exclusively cells with round granules were found. In young rats, chronic treatment with a low dose (0.01 mg/kg/day) of apomorphine did not result in a significant change in plasma PRL level or cell morphology. However, high dose (0.25 mg/kg/day) of apomorphine resulted in a significant decrease in plasma PRL levels, a decrease of number of cells with polymorphic granules and an increase of cells with round granules. The occurrence of PRL cells with round granules and plasma levels was negatively correlated. In aged rats, apomorphine (0.01 or 0.25 mg/kg/day) treatment did not affect plasma levels nor did it affect the distribution of the cell types. We conclude that in young rats PRL cells are sensitive to apomorphine and that their ultrastructure reflects a phase of the secretory cycle. In aged rats, the cells appear to have lost their sensitivity to apomorphine. The fact, that the distribution over the different cell types in control aged rats is similar to that of the apomorphine-treated young rats, suggests a strong influence of endogenous dopamine on PRL cell physiology in the aged rat.

Animals↗
PubMed1981

Pharmacokinetic study of apomorphine-induced stereotypy in food deprived rats.

The relationship between the effect of food deprivation on apomorphine-induced stereotypy and the plasma apomorphine concentration in rats was studied. Male Wistar rats, allowed to have free access to food and water on deprived of food for 48 hr, were injected subcutaneously with apomorphine hydrochloride (10 mg/kg). Food deprivation was liable to potentiate the apomorphine-induced stereotypy in the early stage after dosing. Higher plasma apomorphine concentrations were found in the food deprived rats at this observation period. The potentiation of apomorphine-induced stereotypy following food deprivation can in part be explained by the pharmacokinetics changes. The exact mechanism of the effect of food deprivation on apomorphine kinetics is not clear at present.

Animals↗
PubMed1988

Locomotor activity and stereotypy in rats following repeated apomorphine treatments at 1-, 3-, or 7-day intervals.

In two experiments, the effects of repeated intermittent administration of a relatively high dose of apomorphine (5 mg/kg) on locomotor activity and/or stereotypic behavior in rats was determined. In Experiment 1, male rats were given ten subcutaneous (SC) injections of apomorphine or vehicle and tested for locomotor activity and stereotypy. The first nine injection test sessions were given at 3-day intervals and the tenth injection test session was given 18 days following the ninth session. In Experiment 2, male rats were tested for locomotor activity following ten SC injections of apomorphine or vehicle with either a one- or seven-day interval between injections. Major findings were as follows: a) apomorphine produced progressively greater increases in locomotor activity with each succeeding injection (i.e., sensitization); b) sensitization to the locomotor activity stimulating effects of apomorphine developed with interinjection intervals of one, three, and seven days; c) the sensitization effect was maintained over the 18-day drug-free break; and d) the effect of apomorphine on stereotypic behavior did not significantly change with repeated injections. These findings indicate that even a single dose of apomorphine induces relatively long-lasting neurobiological changes. Moreover, these findings are consistent with the view that separate neural pathways mediate locomotor activity and stereotypy in rats.

Age Factors↗
PubMed1993

Long-term sensitization of apomorphine-induced rotation behavior in rats with dopamine deafferentation or excitotoxin lesions of the striatum.

Following unilateral 6-hydroxydopamine (6-OHDA)-induced deafferentation or unilateral kainic acid (KA) lesions of the striatum, rats displayed rotation behavior in response to apomorphine (0.25 or 1 mg/kg, SC, for 6-OHDA- and KA-lesioned rats, respectively). Three days following the initial apomorphine injection, rats were challenged under identical conditions with the same dose of apomorphine received previously. A third trial with apomorphine was again repeated after 3 days. Two more sets of behavioral data, each consisting of three trials, were collected under the same conditions as the first. Each set was separated by a period of 5-6 weeks. Following the second trial of the first set, rats showed a significant increase in the maximal number of rotations, demonstrating behavioral sensitization. Following the two 5-week intervals, rats were still sensitized to apomorphine, showing behavioral responses similar to the sensitized. Following the two 5-week intervals, rats were still sensitized to apomorphine, showing behavioral responses similar to the sensitized responses observed after the initial trials. Thus, the postsynaptically mediated sensitization of apomorphine-induced rotation behavior in 6-OHDA- or KA-lesioned rats is a long-lasting phenomenon. That lesions producing postsynaptic dopaminergic hypersensitivity and hyposensitivity can both show long-lasting sensitization may indicate multiple mechanisms underlying the sensitization.

Animals↗
PubMed1988

Effect of intracaudate haloperidol and apomorphine on switching motor patterns upon current behaviour of cats.

Previous studies using various experimental set-ups, have shown that the dopaminergic activity in the caudate nucleus (CN) is involved in the organism's ability to switch from one motor or behavioural program to another without the help of external stimuli (switching arbitrarily). The main purpose of the present study was to investigate how arbitrarily switching motor patterns manifests itself in an 'open field situation'. Therefore, the effects of CN application of haloperidol (12.5 micrograms/5 microliter) and apomorphine (0.6 micrograms/5 microliter) were analyzed on the ability to switch from one motor program to any other program in cats habituated to an observation cage. Application of haloperidol decreased switching. In addition the number of distinct motor patterns declined after injecting haloperidol into the CN. The haloperidol-induced effect, however, was not selectively restricted to any particular motor pattern. Switching from one motor pattern to another increased after CN injection of apomorphine. Moreover, the number of distinct motor patterns increased after CN injection of apomorphine. However, the effect of CN application of apomorphine was not selectively restricted to any particular motor pattern. Since previous studies have demonstrated that various expressions of dopaminergic CN activity are funnelled through the deeper layers of the superior colliculus (dl-SC), it was hypothesized that switching induced by CN application of apomorphine may also be channelled through the dl-SC. Therefore the effect of dl-SC-injected muscimol (75 ng/1 microliter) was analyzed on the ability to switch motor programs in cats pretreated with apomorphine. Injection of muscimol into the dl-SC reduced both the number of distinct motor patterns and the number of switchings in cats pretreated with apomorphine.

Animals↗
PubMed1989

Opposing effect of apomorphine on antinociceptive activity of morphine: a dose-dependent phenomenon.

Apomorphine, when administered intracerebroventricularly (0.05 mg/kg) to rats, increased tail-flick latency (a spinal nociceptive response). However, intraperitoneal administration at doses of 1, 3 and 10 mg/kg had no effect, probably because of a tonic supraspinal inhibitory influence on spinal dopaminergic neurones involved in segmental nociceptive processes. Depending on the doses administered, intraperitoneal administration of apomorphine exhibited opposite effects on antinociceptive activity of morphine. Pretreatment with a low dose of apomorphine (1 mg/kg) attenuated, whereas, a high dose (10 mg/kg) potentiated morphine-induced antinociception. Dopamine antagonists, in doses that preferentially block autoreceptors, i.e., haloperidol (0.1 mg/kg, i.p.) and (-)-sulpiride (5 mg/kg, i.p.), antagonised the attenuation of morphine antinociception by a low dose of apomorphine, while treatment with a high dose of haloperidol (1 mg/kg, i.p.) and pimozide (1.25 mg/kg, i.p.) completely antagonised the potentiating effect of a high dose of apomorphine on the antinociceptive activity of morphine. The attenuation of morphine antinociception thus appears to be due to decreased dopaminergic activity as a result of preferential dopamine autoreceptor stimulation by a low dose of apomorphine, whereas potentiation with a high dose of apomorphine is caused by enhanced dopaminergic activity via postsynaptic receptor stimulation.

Animals↗
PubMed1995

Apomorphine in patients with Parkinson's disease.

We present a review of the recent literature and personal experience with apomorphine in patients with Parkinson's disease. Apomorphine is a potent D1 and D2 dopaminergic agonist. It has a rapid and short duration effect after subcutaneous administration at doses ranging from 15 to 180 micrograms/kg. Plasma maximal concentration is reached in 8-16 minutes, with a plasma half life of 34-70 minutes. Bioavailability is close to 100%. Repeated injections in patients show post-stimulative hyposensitivity. Apomorphine test appears very useful for the differential diagnosis between idiopathic Parkinson's disease and other Parkinson plus syndromes, and as a predictive test for dopaminergic responsiveness. Appropriate doses are able to alleviate akinesia, rigidity and tremor. Recent therapeutic trials have demonstrated the high interest of intermittent multiple subcutaneous apomorphine injections to cut the "off" motor phases in fluctuating parkinsonian patients under chronic levodopa treatment. In some cases, continuous apomorphine subcutaneous infusion with a portable pump may be required, particularly when levodopa treatment is temporarily interrupted, as after abdominal surgery. During long-term treatment, the apomorphine dose able to relieve akinesia remains stable. Peripheral side effects such as nausea and hypotension may be prevented by the co-administration of domperidone, a peripheral dopaminergic antagonist. Cutaneous fibrous nodules and psychiatric symptoms may occur, but usually at high dosages with continuous infusion. Local allergic effects have limited the use of other routes of administration, such as intranasal, sublingual, and rectal routes. Apomorphine is also used as a pharmacological tool for clinical research with the aim of a better understanding of the pathophysiology of Parkinson's disease.

Antiparkinson Agents↗
PubMed2003

Oxidative damage in brains of mice treated with apomorphine and its oxidized derivative.

Increasing evidence suggests that some of the neurobiological and neurotoxic actions of apomorphine and other dopamine receptor agonists might be mediated by their oxidation derivatives. The aim of the present study was to evaluate the effects of apomorphine and its oxidation derivative, 8-oxo-apomorphine-semiquinone (8-OASQ), on oxidative stress parameters and antioxidant enzyme activity. Adult male CF-1 mice were treated with a systemic injection of apomorphine (0.4, 4.0 or 40.0 mg/kg) or 8-OASQ (0.4, 4.0 or 40.0 mg/kg). Animals were sacrificed by decapitation 24 h after treatment, and the forebrains were collected for analysis of thiobarbituric acid reactive species, protein carbonyls, the total radical-trapping antioxidant parameter, catalase and superoxide dismutase. These treatments did not induce lipid peroxidation at any dose tested. In contrast, apomorphine induced an increase in protein carbonylation and a decrease in total radical-trapping antioxidant parameter at all doses tested. 8-OASQ induced an increase in protein carbonylation and a decrease in total radical-trapping antioxidant parameter only at the higher dose tested. All apomorphine doses tested induced an increase in catalase, but not superoxide dismutase activities. In contrast, 8-OASQ induced a dose-dependent increase in CAT activity. The results suggest that apomorphine and its oxidation product, 8-OASQ, induce differential effects on CNS oxidative parameters.

Animals↗
PubMed2004

The effect of SR 141716 and apomorphine on sensorimotor gating in Swiss mice.

The aim of the present study was to investigate in Swiss mice the acute effects of the CB(1) receptor antagonist N-piperidino-5-(4-chlorphenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR 141716) alone and in combination with apomorphine, a D(1)/D(2) receptor agonist, on prepulse inhibition (PPI) of the acoustic startle response, an operational measure of sensorimotor gating. SR 141716 (1 and 3 mg/kg i.p.) had no significant effect on PPI. Apomorphine (3 mg/kg i.p.) significantly disrupted PPI. The PPI of mice injected with SR 141716 (1 mg/kg i.p.) plus apomorphine (3 mg/kg i.p.) was not significantly different to that of vehicle plus apomorphine (3 mg/kg i.p.)-treated mice. However, the higher dose of SR 141716 used (3 mg/kg i.p.) significantly inhibited the disruption of PPI produced by apomorphine. These results suggest that antagonism of CB(1) receptors with SR 141716 has no significant effect on sensorimotor gating in Swiss mice. However, CB(1) receptors appear to be important in the effect of apomorphine on sensorimotor gating, as antagonism of CB(1) receptors with SR 141716 inhibits apomorphine-induced disruptions.

Animals↗