The role of dopamine in the discriminative stimulus properties of cocaine

McKenna, Mary; Ho, Beng T.

doi:10.1016/0028-3908(80)90153-7

Cited by 98 publications

(45 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, sigma 1 receptor antagonists could prevent the cocaine-induced CPP by provoking amnesia. Cocaine is known to produce a strong mnesic imprint in the brain, sustaining not only the place preference mechanisms, but also the state-dependence (Maurice et al 2001) and drug discrimination properties of the drug (McKenna and Ho 1980). Amnesic drugs, by blocking the chemical mnesic imprint of cocaine, may allow disruption of the environmental association necessary to develop the CPP behavior and would lead to similar results as observed in this study.…”

Section: Discussionsupporting

confidence: 79%

Involvement of the Sigma1 Receptor in Cocaine-induced Conditioned Place Preference Possible Dependence on Dopamine Uptake Blockade

Romieu

Phan

Martin‐Fardon

et al. 2002

Neuropsychopharmacology

118

138

View full text Add to dashboard Cite

The involvement of the sigma 1 receptor on the rewarding effects of cocaine was examined using the conditioned place preference (CPP) procedure in C57BL/6 mice. Acquisition or expression of cocaine (20 mg/kg i.p.)-induced CPP was significantly decreased by pre-treatment with the selective sigma 1 receptor antagonists N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine (NE-100) or N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047), 1-10 mg/kg, i.p. The sigma 1 receptor agonists igmesine or 2-(4-morpholinoethyl-1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084) failed to induce CPP when injected alone. Moreover, the CPP induced by N-[1-(2-benzo(b)Cocaine is a highly addictive substance that is abused by humans worldwide (Warner 1993;Higgins 1997). Cocaine also acts as a potent reinforcer in laboratory animals (Pickens and Thompson 1968;Koob 1992;Stolerman 1992;Woolverton and Johnson 1992). While cocaine inhibits the transport of serotonin (5-HT), norepinephrine and dopamine (DA), it is widely accepted that the ad- NO . 4 Sigma 1 Receptor and Cocaine 445 dictive and reinforcing actions of cocaine are dependent on the drug's ability to block the dopamine transporter (DAT), thereby increasing dopamine (DA) neurotransmission (Kuhar 1992;Ritz et al. 1987;Parsons et al. 1998;Woolverton 1992). Because of the link between cocaine's addictive liability and the DA reward/reinforcement circuitry of the forebrain (Koob 1992), treatment strategies against cocaine abuse have logically targeted the DA system. However, it has been described that cocaine also interacts with the sigma 1 receptor at a similar dose range as observed for the DAT and that the sigma 1 receptor is implicated in some of cocaine's effects such as locomotor activation, sensitization, convulsion and lethality (Koe 1976;Reith et al. 1986;Menkel et al. 1991;Ujike et al. 1992;Ritz and George 1993). Therefore, the diverse pharmacological profile of cocaine may contribute to, or modulate, its behavioral effects through a complex mechanism of action affecting the different monoaminergic transporters as well as other targets. Consistent with this hypothesis is the study by Sora et al. (2000) demonstrating that it is possible to establish cocaineinduced place preference in DA or 5-HT transporter knockout mice, leading to the hypothesis that other targets might be involved in producing the rewarding effects of cocaine. An alternative therapeutic approach to treating cocaine addiction, therefore, would be to target the sigma 1 receptor, which has recently been demonstrated to be involved in cocaine's rewarding effects measured using a conditioned place preference (CPP) paradigm in mice (Romieu et al. 2000). The sigma 1 receptor, localized intracellularly within the neurons, is a 223 amino acid protein, cloned in several animal species and humans (Hanner et al. 1996;Kekuda et al. 1996;Seth et al. 1997Seth et al. , 1998Pan et al. 1998). The receptor appeared devoid of analogy with any other known mammalian protein and its ...

show abstract

Section: Discussionsupporting

confidence: 79%

Involvement of the Sigma1 Receptor in Cocaine-induced Conditioned Place Preference Possible Dependence on Dopamine Uptake Blockade

Romieu

Phan

Martin‐Fardon

et al. 2002

Neuropsychopharmacology

118

138

View full text Add to dashboard Cite

show abstract

“…Experimental studies have found that cocaine functions as a discriminative stimulus in animals (Woolverton and Trost, 1978). Additionally, studies have con®rmed a prominent role for dopamine (McKenna and Ho, 1980) and a supportive role for D 1 dopamine receptors in mediating the discriminative stimulus effect of cocaine. For example, a number of investigations have found that pretreatment with D 1 receptor antagonists attenuate the discriminative stimulus effects of cocaine (Kleven et al, 1988(Kleven et al, , 1990aBarrett and Appel, 1989;Callahan et al, 1991;Sinnott and Nader, 2001).…”

Section: Receptors Mediate Cocaine-induced Behaviorsmentioning

confidence: 99%

D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action

Hummel

Unterwald

2002

Journal Cellular Physiology

View full text Add to dashboard Cite

Cocaine is one of the most abused psychostimulants known to man and as such, researchers have been steadfast in their attempts to understand the neurobiological mechanisms responsible for its abuse. Cocaine undoubtedly wreaks havoc on a number of mammalian neuronal neurotransmitter systems, and it is maintained that this dysregulatory effect supports cocaine abuse. Cocaine's mechanism of action has been well described. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the reuptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons (Heikkila et al., 1975, Biochem Pharmacol 24(8):847±852;Reith et al., 1986, Biochem Pharmacol 35(7):1123±1129; Ritz et al., 1987, Science 237:1219± 1223. Inhibition of re-uptake subsequently elevates the synaptic concentrations of each of these neurotransmitters. In addition to this direct effect, cocaine also produces a number of indirect actions, which alter other neuromodulatory systems (i.e., opioidergic, glutamatergic, and GABAergic systems). Many of these effects are just beginning to be elucidated, but nonetheless contribute to this agent's diverse pharmacological pro®le. Interestingly, it is the indirect actions of this melli¯uous molecule, which mediate most of its sought and unsought effects. The intricacy with which cocaine produces neuronal alterations beyond its direct effects on neurotransmitter re-uptake appear to be most relevant to cocaine abuse, and hence the phenomenon of addiction. In light of cocaine's multifarious effects on numerous neuronal systems, its effect on dopaminergic neurotransmission has attracted the most attention, particularly because of the implicated role of dopamine in brain reward. Pharmacologically, the psychostimulant effects of cocaine appear to be mediated by its ability to enhance dopaminergic activity within the mesocorticolimbic circuit (Roberts et al., 1977, Pharmacol Biochem Behav 6(6):615±620). Additionally, it is the intensity with which cocaine produces alterations in dopaminergic circuitry that have enabled this drug to prevail as one of the most addictive substances known to man. This review will summarize ®ndings relevant to cocaine-induced alterations in dopaminemediated signal transduction. Speci®cally, it will concentrate on the D 1 dopamine receptor and intracellular signaling mediated by this receptor subtype. It will describe cocaine-induced cellular and behavioral alterations relevant to this pathway and how these changes potentially effect gene transcription and protein expression. This article too will review a common behavioral manifestation associated with repeated cocaine exposure, sensitization, and why the D 1 dopamine receptor and its associated signaling pathway have been implicated in this phenomenon. Lastly, this article will discuss how targeting the D 1 dopamine receptor and its signaling pathway may offer some insight into understanding cocaine addiction, a somewhat elusive brain disease.

show abstract

“…A previous study showed that bupropion and methylphenidate substitute for the discriminative stimulus effects of cocaine in rats (Awasaki et al, 2011). Hence, it has been well recognized that activation of the dopaminergic system is involved in the discriminative stimulus effects of psychostimulants (Ho and Huang, 1975;McKenna and Ho, 1980;Nielsen et al, 1989;Cunningham et al, 1992), and we believe that activation of the dopaminergic system plays a key role in the discriminative stimulus effects of methylphenidate. However, the dopamine receptor agonist apomorphine did not substitute for the discriminative stimulus effects of methylphenidate, even though at lower doses it completely substituted for the discriminative stimulus effects of other psychostimulants, such as methamphetamine and cocaine, under the exact same conditioning scheme (Suzuki et al, 1997b).…”

Section: Discussionmentioning

confidence: 99%

Differential Substitution for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine and Methylphenidate in Rats

Mori

Uzawa

Kazawa

et al. 2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Previous studies have demonstrated that methylphenidate, MDMA (3,4-methylenedioxymethamphetamine), and other psychostimulants exert stimulant-like subjective effects in humans. Furthermore, MDMA and methylphenidate substitute for the discriminative stimulus effects of psychostimulants, such as amphetamine and cocaine, in animals, which suggests that MDMA and methylphenidate may produce similar discriminative stimulus effects in rats. However, there is no evidence regarding the similarities between the discriminative stimulus effects of MDMA and methylphenidate. To explore this issue, cross-substitution, substitution, and combination tests were conducted in rats that had been trained to discriminate between MDMA (2.5 mg/kg) or methylphenidate (5.0 mg/kg) and saline. In the cross-substitution tests, MDMA and methylphenidate did not cross-substitute for each other. In the substitution test, methamphetamine substituted for the discriminative stimulus effects of methylphenidate, but not for those of MDMA. Furthermore, ephedrine and bupropion, which activate dopaminergic and noradrenergic systems, substituted for the discriminative stimulus effects of methylphenidate. On the other hand, serotonin (5-HT) receptor agonists 5-HT 1A and 5-HT 2 fully substituted for the discriminative stimulus effects of MDMA. These results suggest that activation of the noradrenergic and dopaminergic systems is important for the discriminative stimulus effects of methylphenidate, whereas activation of the serotonergic system is crucial for the discriminative stimulus effects of MDMA. Even though MDMA, like psychostimulants, exerts stimulant-like effects, our findings clearly indicate that the discriminative stimulus effects of MDMA are distinctly different from those of other psychostimulants in rats.

show abstract

The role of dopamine in the discriminative stimulus properties of cocaine

Cited by 98 publications

References 28 publications

Involvement of the Sigma1 Receptor in Cocaine-induced Conditioned Place Preference Possible Dependence on Dopamine Uptake Blockade

Involvement of the Sigma1 Receptor in Cocaine-induced Conditioned Place Preference Possible Dependence on Dopamine Uptake Blockade

D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action

Differential Substitution for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine and Methylphenidate in Rats

Contact Info

Product

Resources

About

The role of dopamine in the discriminative stimulus properties of cocaine

Cited by 98 publications

References 28 publications

Involvement of the Sigma1 Receptor in Cocaine-induced Conditioned Place Preference Possible Dependence on Dopamine Uptake Blockade

Involvement of the Sigma1 Receptor in Cocaine-induced Conditioned Place Preference Possible Dependence on Dopamine Uptake Blockade

D1 dopamine receptor: A putative neurochemical and behavioral link to cocaine action

Differential Substitution for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine and Methylphenidate in Rats

Contact Info

Product

Resources

About

D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action