Reinforcing effect of the D1 dopamine agonist SKF 81297 in rhesus monkeys

Weed, Michael R.; Vanover, Kimberly E.; Woolverton, William L.

doi:10.1007/bf02244333

Cited by 90 publications

(80 citation statements)

References 4 publications

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“…In a self-administration study in rhesus monkeys maintained by baseline cocaine, three of the six monkeys self-administered the high ef®cacy D 1 agonists SKF 81297, SKF 82958, R ( ) 6-Br-APB, whereas no monkey self-administered the low ef®cacy agents SKF 38393, SKF 77434, and S (À) 6-Br-APB (Weed and Woolverton, 1995). These ®ndings substantiate previous work indicating D 1 dopamine receptor involvement in cocaine reinforcement (Weed et al, 1993). Additionally, they suggest that intrinsic ef®cacy may affect a ligand's ability to reinforce behavior.…”

Section: Receptors Mediate Cocaine-induced Behaviorssupporting

confidence: 89%

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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Section: Receptors Mediate Cocaine-induced Behaviorssupporting

confidence: 89%

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

Hummel

Unterwald

2002

Journal Cellular Physiology

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“…One explanation for this observation is that SKF 81297 substituted for the pharmacological actions of cocaine in these animals and, thereby, decreased or eliminated cocaine-seeking behavior. This interpretation is consistent with reports that D 1 agonists can substitute for the reinforcing effects of cocaine in rhesus monkeys (Weed et al 1993(Weed et al , 1997Weed and Woolverton 1995) and effectively block drugseeking behavior induced by cocaine priming injections in rats, presumably as a result of their cocaine-like pharmacological action (Self et al 1996). In rats that showed an augmented behavioral response to the cocaine S ϩ after SKF 81297, responding was vigorous and sustained throughout the session.…”

supporting

confidence: 90%

Enduring Resistance to Extinction of Cocaine-Seeking Behavior Induced by Drug-Related Cues

Weiss

2001

Neuropsychopharmacology

183

131

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The conditioning of cocaine's pharmacological actions with environmental stimuli is thought to be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of environmental stimuli in enduring vulnerability to relapse, the resistance to extinction of drug-seeking behavior elicited by a cocainerelated stimulus was examined. Male Wistar rats were trained to associate discriminative stimuli (S D ) with the availability of intravenous cocaine (S ϩ ) vs. the availability of non-rewarding (S Ϫ)Cocaine addiction is a chronic relapsing disorder (Leshner 1997;O'Brien et al. 1998;O'Brien and McLellan 1996). Relapse prevention has therefore emerged as a central issue in treatment and medications development efforts (Carroll et al. 1991;DeLong 1994; O'Brien 362 F. Weiss et al. N EUROPSYCHOPHARMACOLOGY 2001 -VOL . 25 , NO . 3 and McLellan 1996). A wealth of clinical studies point towards drug-related stimuli or events as a critical factor in the long-lasting compulsion to abuse drugs. This literature suggests that environmental stimuli repeatedly paired with the subjective actions of cocaine throughout an individual's history of drug abuse can produce intense drug craving (Childress et al. 1988;Ehrman et al. 1992;Kilgus and Pumariega 1994;Robbins et al. 1997;Satel et al. 1995;Wallace 1989) or elicit automatic behavioral responses (Miller and Gold 1994;Tiffany and Carter 1998) that may lead to relapse.Consistent with a role of conditioning factors in the resumption of drug abuse habits, several studies in animals have demonstrated that drug-associated stimuli can elicit a transient recovery of extinguished responding at a lever previously associated with cocaine selfadministration (e.g., deWit and Stewart 1981;Fuchs et al. 1998). However, little information is available, to date, about the persistence of cue-induced drug-seeking behavior. In recent work that has begun to address this issue, appreciable cued recovery of cocaine-seeking behavior was observed when rats were presented with cocaine cues on two separate occasions spaced 20 days apart. Similarly, the efficacy of a cocaine cue to reinstate extinguished cocaine-seeking behavior was found to persist for up to eight days of intermittent testing . The latter study revealed also that cocaine cues increase extracellular dopamine levels in the nucleus accumbens and amygdala. These findings indicate that the behavioral effects of cocaine-related environmental stimuli can show resistance to extinction, and that their motivating effects may involve activation of forebrain DA neurotransmission.Considering the mounting evidence that learned responses to cocaine-related stimuli represents a significant factor in long-lasting relapse risk (see O'Brien et al. 1998 for review), better understanding of the environmental, behavioral, and neuropharmacological bases of this phenomenon will be of substantial clinical benefit. The purpose of the present study was to characterize the resistance to extinction of cocaine-seeking behav...

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“…First, there has been growing interest in the D 1 receptor as a target for pharmacotherapies for stimulant dependence in humans (Haney et al, 1999(Haney et al, , 2001Romach et al, 1999). Second, although D 1 -like and D 2 -like receptors have both been implicated in the discriminative and reinforcing effects of cocaine in rats and primates (Woolverton et al, 1984;Bergman et al, 1990;Kleven et al, 1990;Spealman et al, 1991;Witkin et al, 1991;Self and Stein, 1992;Koob, 1993, 1994;Weed and Woolverton, 1995), important differences in the effects produced by stimulating D 1 and D 2 receptors have been observed (Grech et al, 1996;Self et al, 1996;Caine et al, 1999aCaine et al, , 2000aKhroyan et al, 2000). Third, D 2 receptor knock-out mice acquired cocaine self-administration (Caine et al, 2002), suggesting that receptors other than D 2 were sufficient to mediate the reinforcing effects of cocaine.…”

Section: Introductionmentioning

confidence: 43%

Lack of Self-Administration of Cocaine in Dopamine D₁Receptor Knock-Out Mice

Caine¹,

Thomsen²,

Gabriel³

et al. 2007

J. Neurosci.

168

134

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Evidence suggests a critical role for dopamine in the reinforcing effects of cocaine in rats and primates. However, self-administration has been less often studied in the mouse species, and, to date, "knock-out" of individual dopamine-related genes in mice has not been reported to reduce the reinforcing effects of cocaine. We studied the dopamine D 1 receptor and cocaine self-administration in mice using a combination of gene-targeted mutation and pharmacological tools. Two cohorts with varied breeding and experimental histories were tested, and, in both cohorts, there was a significant decrease in the number of D 1 receptor knock-out mice that met criteria for acquisition of cocaine self-administration (

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Reinforcing effect of the D1 dopamine agonist SKF 81297 in rhesus monkeys

Cited by 90 publications

References 4 publications

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

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

Enduring Resistance to Extinction of Cocaine-Seeking Behavior Induced by Drug-Related Cues

Lack of Self-Administration of Cocaine in Dopamine D₁Receptor Knock-Out Mice

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Reinforcing effect of the D1 dopamine agonist SKF 81297 in rhesus monkeys

Cited by 90 publications

References 4 publications

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

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

Enduring Resistance to Extinction of Cocaine-Seeking Behavior Induced by Drug-Related Cues

Lack of Self-Administration of Cocaine in Dopamine D1Receptor Knock-Out Mice

Contact Info

Product

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About

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

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

Lack of Self-Administration of Cocaine in Dopamine D₁Receptor Knock-Out Mice