Comparison of dopamine receptor antagonists on hyperlocomotion induced by cocaine, amphetamine, MK-801 and the dopamine D 1 agonist C-APB in mice

O’Neill, Michael F.; Shaw, Gillian

doi:10.1007/s002130051055

Cited by 108 publications

(73 citation statements)

References 25 publications

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“…The observations that GS39783, in contrast to baclofen, does not alter baseline locomotor activity is in agreement with the lack of effects in other behavioral tests in both rats and mice, which are sensitive to baclofen administration; these include the rotarod motor coordination task, cognitive tasks, and hypothermia measurements Jacobson and Cryan, 2005). Of note, the effects of GABA B receptor ligands on cocaine-induced hyperactivity appear not as robust as that reported with D1-selective DA receptor antagonists such as SCH23390, which almost completely block the locomotor stimulant effects of cocaine (O'Neill et al, 1999;Adams et al, 2001). However, a thorough evaluation of GABA B receptor-positive modulators in comparison to other drugs attenuating locomotor stimulant effects of cocaine requires sideby-side experiments and a careful investigation of their side-effect profile, which may influence locomotor-based behavioral readouts.…”

Section: Discussionsupporting

confidence: 77%

GABAB Receptor-Positive Modulation Decreases Selective Molecular and Behavioral Effects of Cocaine

Lhuillier

Mombereau

Cryan

et al. 2006

Neuropsychopharmacol

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Exposure to cocaine induces selective behavioral and molecular adaptations. In rodents, acute cocaine induces increased locomotor activity, whereas prolonged drug exposure results in behavioral locomotor sensitization, which is thought to be a consequence of druginduced neuroadaptive changes. Recent attention has been given to compounds activating GABA B receptors as potential antiaddictive therapies. In particular, the principle of allosteric positive GABA B receptor modulators is very promising in this respect, as positive modulators lack the sedative and muscle relaxant properties of full GABA B receptor agonists such as baclofen. Here, we investigated the effects of systemic application of the GABA B receptor-positive modulator GS39783 (N,N 0 -dicyclopentyl-2-methylsulfanyl-5-nitropyrimidine-4, 6-diamine) in animals treated with acute and chronic cocaine administration. Both GS39783 and baclofen dose dependently attenuated acute cocaine-induced hyperlocomotion. Furthermore, both compounds also efficiently blocked cocaine-induced Fos induction in the striatal complex. In chronic studies, GS39783 induced a modest attenuation of cocaine-induced locomotor sensitization. Chronic cocaine induces the accumulation of the transcription factor DFosB and upregulates cAMP-response-element-binding protein (CREB) and dopamine-and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32). GS39783 blocked the induction/activation of DARPP-32 and CREB in the nucleus accumbens and dorsal striatum and partially inhibited DFosB accumulation in the dorsal striatum. In summary, our data provide evidence that GS39783 attenuates the acute behavioral effects of cocaine exposure in rodents and in addition prevents the induction of selective long-term adaptive changes in dopaminergic signaling pathways. Further investigation of GABA B receptor-positive modulation as a novel therapeutic strategy for the treatment of cocaine dependence and possibly other drugs of abuse is therefore warranted.

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Section: Discussionsupporting

confidence: 77%

GABAB Receptor-Positive Modulation Decreases Selective Molecular and Behavioral Effects of Cocaine

Lhuillier

Mombereau

Cryan

et al. 2006

Neuropsychopharmacol

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“…In fact, we observed that the dose-response curve for OLDA was bell-shaped, as are those reported for a number of direct and indirect dopaminergic agents (15)(16). Moreover, it is well documented that hyperactivity induced by both direct and indirect DA agonists is blocked by haloperidol (17)(18)(19)(20), a preferential D 2 receptor antagonist (21)(22). In the present study, haloperidol prevented, in a dose-dependent manner, the OLDA-induced hyperlocomotion, not altering basal locomotor activity in well-habituated animals.…”

Section: Discussionsupporting

confidence: 81%

N-Oleoyl-Dopamine Increases Locomotor Activity in the Rat

Przegaliński

Filip²,

Zając

et al. 2006

Int J Immunopathol Pharmacol

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N-oleoyl-dopamine (OLDA), a condensation product of oleic acid and dopamine (DA), is a bioactive lipid whose biological functions are not yet fully explored. The compound crosses the blood-brain barrier and might be considered as a carrier of DA into the brain. In this study we sought to determine whether OLDA would influence locomotor behavior and whether the central DA system would be involved in such influence. We addressed this issue by investigating horizontal locomotor activity in male Wistar rats after intraperitoneal administration of OLDA, 5-20 mg/kg, before and after pretreatment with haloperidol, a D z receptor antagonist. We found that OLDA caused a prompt stimulation of locomotor activity, with a bell-shaped dose-response. The maximum stimulatory effect was observed after 10 mg/kg of OLDA where the mean distance traveled by rats during a 2-hour test increased to 1213 ±196(SE) em from the 403 ±89 em in the vehicle-treated rats (P<0.05). This effect was dose-dependently antagonized by haloperidol (0.1-0.2 mg/kg). The results support the hypothesis that the OLDA-induced hyperlocomotion was mediated by the stimulation of DA systems. Using in vitro assays, we further demonstrated that OLDA is a stable compound that resists hydrolysis over a 2-hour period and thus the integral OLDA compound exerted DA-Iike effects. We conclude that OLDA is a potential brain modifier of motor behavior, the biological consequences of which remain to be explored.

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“…Although neither benzazepine increased horizontal motor activity, others have found increases at doses similar to, or lower than, the lowest dose used in the current experiment (Arnt et al 1992;O'Neill and Shaw 1999). It is possible that the doses used in the current experiment were beyond those that would increase locomotion.…”

Section: Discussionmentioning

confidence: 52%

Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents

Chausmer

Katz

2001

Psychopharmacology

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Rationale: Recent data suggest that dopamine (DA) D 1 -like receptor full agonists may be potential pharmacotherapeutic agents for treating cocaine abuse. The structurally novel isochroman D 1 -like agonist, A-77636, has not been well characterized and may prove to be useful as such an agent. Objectives: The interactions of cocaine and A-77636 were compared to those obtained with the better investigated benzazepine D 1 -like dopamine agonists, SKF 82958 and SKF 81297. The alterations in the locomotor stimulant and discriminativestimulus effects of cocaine by the full D 1 -like dopamine receptor agonists were investigated across a full range of doses in order to characterize their interactions. Methods: Drug-naive Swiss-Webster mice were pretreated with SKF 81297, SKF 82958 or A-77636 (1-10 mg/kg) and cocaine (5-56 mg/kg) prior to a 30-min period in which locomotor activity was assessed. Rats were trained on a fixed ratio 20 (FR20) schedule to discriminate IP saline from cocaine (10 mg/kg) injections. Cocaine alone (1-10 mg/kg) and with either A-77636 (0.56-1.7 mg/kg), SKF 82958 (0.01-0.1 mg/kg) or SKF 81297 (0.1-0.56) were injected IP 5 min prior to a 15-min test session. Results: Cocaine maximally stimulated activity at 20-40 mg/kg with higher and lower doses stimulating activity less. Each D 1 -like agonist produced a dose-related decrease in cocaine-induced locomotor activity and lowered its maximal rate. Each of the D 1 -like agonists partially substituted for cocaine, with maximal substitution approximating 49, 35, and 24% for SKF 81297, SKF 82958, and A-77636, respectively. SKF 82958 significantly shifted the cocaine dose-effect curve approximately 3-fold to the left. With SKF 81297, there was a trend towards a leftward shift of cocaine dose effects, however the change was not statistically significant. In contrast to the other two D 1 -like agonists, A-77636 either did not affect the cocaine dose-effect curve or shifted it to the right. Conclusions: All three agonists produced similar effects on cocaine-induced locomotor activity, however the discriminative-stimulus effects of cocaine were affected differently by the D 1 agonists. These results suggest fundamental differences in the actions of these D 1 agonists. Because A-77636 consistently attenuated the present effects of cocaine, it may prove more useful than the others as a pharmacotherapy to treat cocaine abuse.

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Comparison of dopamine receptor antagonists on hyperlocomotion induced by cocaine, amphetamine, MK-801 and the dopamine D 1 agonist C-APB in mice

Abstract: The results of the present study suggest that selective blockade of D1 receptors suppresses amphetamine and cocaine-induced hyperactivity in mice but not MK-801-induced locomotor activity.

Cited by 108 publications

References 25 publications

GABAB Receptor-Positive Modulation Decreases Selective Molecular and Behavioral Effects of Cocaine

GABAB Receptor-Positive Modulation Decreases Selective Molecular and Behavioral Effects of Cocaine

N-Oleoyl-Dopamine Increases Locomotor Activity in the Rat

Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents

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