Selective antagonist at D3 receptors, but not non-selective partial agonists, influences the expression of cocaine-induced conditioned place preference in free-feeding rats

Cervo, Luigi; Burbassi, Silvia; Čolović, Milena; Caccia, Silvio

doi:10.1016/j.pbb.2005.11.015

Cited by 34 publications

(30 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously described (Cervo et al, 2002(Cervo et al, , 2005, on the first day, before any drug treatment, each rat was allowed to explore the apparatus for 15 minutes, and the time spent in the three compartments was recorded. Rats were then assigned to treatment groups and conditioning compartments, ensuring that all treatments were matched as closely as possible between compartments.…”

Section: Cppmentioning

confidence: 99%

“…Rats were then assigned to treatment groups and conditioning compartments, ensuring that all treatments were matched as closely as possible between compartments. The schedule during the conditioning phase consisted of an intraperitoneal injection of cis-4,49-DMAR and cocaine or vehicle on alternate days, with a 24-hour interval between conditioning days; this did not influence CPP in our experimental conditions (Cervo et al, 2002(Cervo et al, , 2005.…”

Section: Cppmentioning

confidence: 99%

“…These schedules were selected on the basis of data in Fig. 4 for 4,49-DMAR and published data for cocaine (Cervo et al, 2002(Cervo et al, , 2005, and they allowed the rats to be exposed at the drugs' peak effect.…”

Section: Cppmentioning

confidence: 99%

See 2 more Smart Citations

Brain Disposition of cis-para-Methyl-4-Methylaminorex (cis-4,4′-DMAR) and Its Potential Metabolites after Acute and Chronic Treatment in Rats: Correlation with Central Behavioral Effects

Lucchetti

Marzo

Passoni

et al. 2017

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

para-Methyl-4-methylaminorex (4,49-DMAR) is a phenethylamine derivative with psychostimulant activity whose abuse has been associated with several deaths and a wide range of adverse effects. We recently validated a high-performance liquid chromatography-tandem mass spectrometry method to measure the compound's concentrations in plasma, and we applied it to describe the pharmacokinetic properties of 4,49-DMAR after a single dose in rats. In this study, we investigated the brain disposition and metabolism of cis-4,49-DMAR after intraperitoneal injection as well as its central behavioral effects. Locomotor activity increased after a single injection of 10 mg/kg, peaking at 2 hours and disappearing at 5 hours; in these conditions, brain absorption was very rapid, (t max 5 30-60 minutes) and large (brain-to-plasma ratio 5 24); the half-life was approximately 50 minutes. After 14 daily doses, the compound's effect on locomotor activity was greater (approximately 20% compared with the effect after the first dose), but not for pharmacokinetic reasons. Using high-resolution mass spectrometry, we also identified four metabolites of cis-4,49-DMAR in the plasma and brain of treated rats. Semiquantitative analysis indicated low brain permeability and very low brain concentrations, suggesting that these metabolites do not contribute to central behavioral effects; however, the metabolite originating from oxidation of the paramethyl group (M2) persisted in the plasma longer and at higher concentrations than the parent molecule and could be used to evaluate drug intake in human consumers. Finally, we describe the rewarding effect of cis-4,49-DMAR in the conditioning place preference test, suggesting a high risk of addiction in humans.

show abstract

Section: Cppmentioning

confidence: 99%

Section: Cppmentioning

confidence: 99%

See 1 more Smart Citation

Brain Disposition of cis-para-Methyl-4-Methylaminorex (cis-4,4′-DMAR) and Its Potential Metabolites after Acute and Chronic Treatment in Rats: Correlation with Central Behavioral Effects

Lucchetti

Marzo

Passoni

et al. 2017

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Gyertyan et al (2007) reported that the novel Drd3 partial agonist RGH-237 at 10 but not 30 mg/kg blocked acquisition of a cocaine CPP but they ascribed no biological importance to this observation. The Drd3 antagonist SB-277011-A blocked expression of a CPP based on cocaine (Vorel et al, 2002;Cervo et al, 2005); the partial agonist BP 897 blocked expression in one study (Duarte et al, 2003) but not in another (Cervo et al, 2005). Thus, a number of (but not all) studies have found that a Drd3 antagonist or partial agonist blocks the expression of CPP based on cocaine.…”

Section: Drd3 Antagonists and Conditioned Place Preference (Cpp)mentioning

confidence: 96%

“…Vorel et al (2002) and Duarte et al (2003) reported that SB-277011-A and BP 897 blocked both the acquisition and expression of a CPP based on cocaine. Alternatively, others have reported no significant effect of the Drd3 agents, SB-277011-A or BP 897 on the acquisition of a CPP based on cocaine (Gyertyan and Gal, 2003;Cervo et al, 2005). Gyertyan et al (2007) reported that the novel Drd3 partial agonist RGH-237 at 10 but not 30 mg/kg blocked acquisition of a cocaine CPP but they ascribed no biological importance to this observation.…”

Section: Drd3 Antagonists and Conditioned Place Preference (Cpp)mentioning

confidence: 99%

Dopaminergic mechanism of reward-related incentive learning: Focus on the dopamine d3 receptor

Beninger

Banasikowski

2008

neurotox res

View full text Add to dashboard Cite

Dopamine D(3) receptors (Drd3) have been implicated in the control of responding by drug-related conditioned incentive stimuli. We review recent studies of the effects of Drd3 antagonists or partial agonists on the control of self-administration of intravenous (IV) cocaine, IV morphine and oral ethanol on reward-rich and lean schedules, in reinstatement tests, on second-order schedules and on the acquisition and expression of conditioned place preference (CPP) and conditioned motor activity. For comparison, related studies where conditioned stimuli are based on nutritional reward also are considered. When self-administration depends more heavily on conditioned cues for its maintenance, for example on second-order schedules or lean ratio schedules, Drd3 antagonists or partial agonists reduce responding. Although data are limited, similar effects may be seen for responding for cues based on drugs or nutritional rewards. Drd3 agents also block the ability of conditioned cues to reinstate responding for cocaine or food. Published results suggest that Drd3 plays a more important role in the expression than in the acquisition of a CPP or conditioned motor activity. The mechanism mediating the role of Drd3 in the control of responding by conditioned incentive stimuli remains unknown but it has been found that Drd3 receptors increase in number in the nucleus accumbens during conditioning. Perhaps Drd3 participates in the molecular mechanisms underlying the role of dopamine and of dopamine receptor subtypes in reward-related incentive learning.

show abstract

Dopamine Receptors: Neurotherapeutic Targets for Substance Use Disorders

Nilson¹,

Felsing²,

Allen³

2022

GPCRs as Therapeutic Targets

View full text Add to dashboard Cite

Selective antagonist at D3 receptors, but not non-selective partial agonists, influences the expression of cocaine-induced conditioned place preference in free-feeding rats

Cited by 34 publications

References 47 publications

Brain Disposition of cis-para-Methyl-4-Methylaminorex (cis-4,4′-DMAR) and Its Potential Metabolites after Acute and Chronic Treatment in Rats: Correlation with Central Behavioral Effects

Brain Disposition of cis-para-Methyl-4-Methylaminorex (cis-4,4′-DMAR) and Its Potential Metabolites after Acute and Chronic Treatment in Rats: Correlation with Central Behavioral Effects

Dopaminergic mechanism of reward-related incentive learning: Focus on the dopamine d3 receptor

Dopamine Receptors: Neurotherapeutic Targets for Substance Use Disorders

Contact Info

Product

Resources

About