Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats

Ushijima, Itsuko; C, Ma; Horita, A.

doi:10.1016/0091-3057(95)00167-u

Cited by 72 publications

(70 citation statements)

References 24 publications

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“…In fact, this finding supports evidence that the VTA is not critically involved in food-primed food-seeking behavior (McFarland and Kalivas, 2001). Another issue to consider is the stereotyped pattern of motor activation induced by cocaine (Ushijima et al, 1995). It is conceivable, for example, that during cocaine SA, lever pressing becomes part of a stereotyped motor response.…”

Section: Discussionsupporting

confidence: 75%

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

Sun

Akins

Mattingly

et al. 2005

Neuropsychopharmacol

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Drug addiction is characterized by compulsive drug-seeking and drug-taking behavior and by a high rate of relapse even after long periods of abstinence. Although the mesocorticolimbic dopamine (DA) pathway is thought to play a critical role in drug craving and relapse, recent evidence also implicates glutamate, an amino acid known to activate DA neurons in the ventral tegmental area (VTA) via ionotropic receptors. To assess whether increased glutamate transmission in the VTA is involved in cocaine-primed drug-seeking behavior, we tested rats in a between-session reinstatement model. They were trained to press a lever for cocaine infusions (0.25 mg/ infusion) accompanied by compound stimuli (light and tone) under a modified fixed-ratio 5 reinforcement schedule. Cocaine-primed reinstatement was conducted after lever pressing was extinguished in the absence of the conditioned stimuli. Blockade of ionotropic glutamate receptors in the VTA by local application of kynurenate (0.0, 1.0, 3.2, and 5.6 mg/side) dose-dependently decreased cocaineprimed reinstatement, whereas sucrose-primed reinstatement of sucrose-seeking behavior was unaffected. In addition, the minimum effective dose for decreasing cocaine-primed reinstatement was ineffective in the substantia nigra. Together, these data indicate that glutamatergic activation of the VTA is critical for cocaine-primed reinstatement. Because such activation can increase impulse flow in DA neurons and thus DA release in mesocorticolimbic targets, this glutamate-DA interaction in the VTA may underlie cocaine-primed relapse to cocaine-seeking behavior.

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Section: Discussionsupporting

confidence: 75%

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

Sun

Akins

Mattingly

et al. 2005

Neuropsychopharmacol

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“…Pre-treatment with SCH 23390 blocked cocaine-induced increases in locomotor activity in rats that were repeatedly administered cocaine, whereas the D 2 receptor antagonists, haloperidol, and raclopride had no such effect (McCreary and Marsden, 1993;Ushijima et al, 1995). Interestingly, pre-treatment with the D 2 receptor agonists, quinpirole and bromocriptine caused cocaine-induced locomotor activity to be replaced with stereotyped behaviors such as snif®ng, licking, and gnawing (Ushijima et al, 1995). Taken together, these data demonstrate a functional role for the D 1 receptor in cocaine-induced locomotion.…”

Section: Receptors Mediate Cocaine-induced Behaviorsmentioning

confidence: 99%

“…A number of studies have shown that D 1 and D 2 dopamine receptors are differentially involved in cocaine-induced changes in locomotor activity. Some maintain that the D 1 receptor may be somewhat more important in this regard (McCreary and Marsden, 1993;Xu et al, 1994;Ushijima et al, 1995). For example, mice pre-treated with the D 1 receptor antagonist, SCH 23390, showed an attenuated locomotor response to cocaine (Cabib et al, 1991).…”

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

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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.

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“…Sulpiride, a D2 receptor antagonist, had no effect on seizures or mortality. Interestingly, sulpride can prevent some of the behavioral effects of cocaine, suggesting that the pharmacologic and toxic effects of cocaine may be due to different dopamine receptor systems [57].…”

Section: Post-receptor Effects Of Cocainementioning

confidence: 99%

Mechanisms of Acute Cocaine Toxicity

Heard¹,

Palmer²,

Zahniser³

2008

TOPHARMJ

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Abstract:Patients with acute cocaine poisoning present with life-threatening symptoms involving several organ systems. While the effects of cocaine are myriad, they are the result of a limited number of cocaine-protein interactions, including monoamine transporter, neurotransmitter receptor and voltage-gated ion channels. These primary interactions trigger a cascade of events that ultimately produce the clinical effects. The purpose of this article is to review the primary interactions of cocaine and the effects that these interactions trigger. We also describe the progression of symptoms observed in cocaine poisoning as they relate to serum cocaine concentrations.

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Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats

Cited by 72 publications

References 24 publications

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

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

Mechanisms of Acute Cocaine Toxicity

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Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats

Cited by 72 publications

References 24 publications

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

Ionotropic Glutamate Receptors in the Ventral Tegmental Area Regulate Cocaine-Seeking Behavior in Rats

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

Mechanisms of Acute Cocaine Toxicity

Contact Info

Product

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About

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