Effects of Cocaine Self-administration on Striatal Dopamine Systems in Rhesus Monkeys Initial and Chronic Exposure

Nader, Michael A.; Daunais, James B.; Moore, Tonya; Nader, Susan H.; Moore, Rodney J.; Smith, Hilary R.; Friedman, David P.; Porrino, Linda J.

doi:10.1016/s0893-133x(01)00427-4

Cited by 192 publications

(180 citation statements)

References 43 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…This is consistent with our previous observation of de novo D1-mediated regulation of GABA transmission in ovBNST neurons of cocaine self-administering rats (Krawczyk et al, 2011b(Krawczyk et al, , 2013. This phenomenon is not unique to the BNST: increase in D1R expression also occurs in the shell of the nucleus accumbens following chronic cocaine self-administration (Nader et al, 2002). Thus, cocaine self-administration may be accompanied by DRD1 gene expression or receptor trafficking to the membrane surface, mechanisms that will require further study.…”

Section: De Novo D1r and D2r In The Ovbnst Of Cocaine Self-administersupporting

confidence: 91%

Dopamine decreases NMDA currents in the oval bed nucleus of the stria terminalis of cocaine self-administering rats

Krawczyk

DeBacker

Mason

et al. 2014

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

Dopamine (DA) and N-methyl-D-aspartate receptors (NMDARs) contribute in the neural processes underlying drug-driven behaviors. DA is a potent modulator of NMDAR, but few studies have investigated the functional interaction between DA and NMDAR in the context of substance abuse. We combined the rat model of cocaine self-administration with brain slice electrophysiology to study DA modulation of NMDA currents in the oval bed nucleus of the stria terminalis (ovBNST), a dense DA terminal field involved in maintenance of cocaine selfadministration amongst other drug related behaviors. Long-Evans rats self-administered intravenous cocaine (0.75 mg/kg/injection) on a progressive ratio (PR) schedule of reinforcement for 15 days and whole-cell patch-clamp recordings were done on the 16th day. DA reduced NMDA currents in brain-slices from cocaine self-administering rats, but not in those of drug-naïve and sucrose self-administering, or when cocaine exposure was passive (yoked), revealing a mechanism unique to voluntary cocaine intake. DA reduced NMDA currents by activating Gprotein-coupled D1-and D2-like receptors that converged on phospholipase C and protein phosphatases. Accordingly, our study reveals a mechanism that may contribute to dysfunctional synaptic plasticity associated with drug-driven behaviors during acute withdrawal.

show abstract

Section: De Novo D1r and D2r In The Ovbnst Of Cocaine Self-administersupporting

confidence: 91%

Dopamine decreases NMDA currents in the oval bed nucleus of the stria terminalis of cocaine self-administering rats

Krawczyk

DeBacker

Mason

et al. 2014

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

show abstract

“…These effects likely involve stress-related circuitry in the extended amygdala, as local infusions of bAR antagonists in the bed nucleus of the stria terminalis (BNST) or in the central nucleus of the amygdala (CeA) also block footshock-induced reinstatement of cocaine SA in rats (Leri et al, 2002). Intriguingly, chronic cocaine SA in rhesus monkeys elevates NET density in the BNST to a greater extent than any reported changes in DAT, D1, or D2 receptors within the striatum of the same monkeys (Letchworth et al, 2001;Nader et al, 2002;Porrino et al, 2002;Macey et al, 2003). Given the known role of NE in central stress responses, these results indicate that NE release in the extended amygdala is required for stress-induced reinstatement.…”

Section: Ne and Psychostimulant Sa: A Reassessmentmentioning

confidence: 98%

There and Back Again: A Tale of Norepinephrine and Drug Addiction

Weinshenker

Schroeder

2006

Neuropsychopharmacol

322

277

View full text Add to dashboard Cite

Fueled by anatomical, electrophysiological, and pharmacological analyses of endogenous brain reward systems, norepinephrine (NE) was identified as a key mediator of both natural and drug-induced reward in the late 1960s and early 1970s. However, reward experiments from the mid-1970s that could distinguish between the noradrenergic and dopaminergic systems resulted in the prevailing view that dopamine (DA) was the primary 'reward transmitter' (a belief holding some sway still today), thereby pushing NE into the background. Most damaging to the NE hypothesis of reward were studies demonstrating that NE receptor antagonists and NE reuptake inhibitors failed to impact drug self-administration. In recent years new tools, such as genetically engineered mice, and new experimental paradigms, such as reinstatement of drug seeking following withdrawal, have propelled NE back into the awareness of addiction researchers. Of particular interest is disulfiram, an inhibitor of the NE biosynthetic enzyme dopamine b-hydroxylase, which has demonstrated promising efficacy in the treatment of cocaine dependence in preliminary clinical trials. The purpose of this review is to synthesize the new data linking NE to critical aspects of DA signaling and drug addiction, with a focus on psychostimulants (eg, cocaine), opiates (eg, morphine), and alcohol.

show abstract

“…Moreover, while lower D 1 receptor responsiveness could underlie higher cocaine intake in animals with prolonged daily access, this effect cannot account for increased cocaine self-administration based on individual differences in our study because D 1 receptor subsensitivity in high intake animals was not evident until later in cocaine withdrawal. However, other studies have reported increases in D 1 receptor binding in several striatal regions 1 day following a shorter period of cocaine self-administration in monkeys (Nader et al, 2002), and functional increases in D 1 receptormediated electrophysiological responses in nucleus accumbens neurons that develop several days after withdrawal from passive cocaine administration in rats (Henry and White, 1991). This latter finding could relate to sensitization of D 1 -mediated behavioral responses in low intake animals, since this effect also required a longer withdrawal period to develop.…”

Section: Brain Cocaine Levelsmentioning

confidence: 98%

“…Although cocaine self-administration produced functional increases in postsynaptic D 2 receptor responses, several studies have found reduced D 2 receptor binding in striatal and other brain regions following chronic psychostimulant use in monkeys and humans (Volkow et al, 1990(Volkow et al, , 1993(Volkow et al, , 2001Moore et al, 1998b;Nader et al, 2002;Martinez et al, 2004), and binge cocaine administration in rats (Maggos et al, 1998). Given that prominent D 2 receptor sensitization develops in both low and high intake groups, and this overall effect was found in a previous study comparing cocaine to saline self-administration (De Vries et al, 2002), it is possible that D 2 receptor sensitization reflects intracellular alterations in D 2 receptor coupling, or an indirect enhancement via perturbations in neural input to D 2 -containing neurons, rather than an increase in D 2 receptor surface expression.…”

Section: Brain Cocaine Levelsmentioning

confidence: 99%

Addiction-Related Alterations in D1 and D2 Dopamine Receptor Behavioral Responses Following Chronic Cocaine Self-Administration

Edwards

Whisler

Fuller

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

The cocaine-addicted phenotype can be modeled in rats based on individual differences in preferred levels of cocaine intake and a propensity for relapse in withdrawal. These cocaine-taking and -seeking behaviors are strongly but differentially regulated by postsynaptic D 1 and D 2 receptors in the mesolimbic dopamine system. Thus, we determined whether addiction-related differences in cocaine selfadministration would be related to differential sensitivity in functional D 1 and D 2 receptor responses. Using a population of 40 outbred Sprague-Dawley rats trained to self-administer cocaine for 3 weeks, we found that animals with higher preferred levels of cocaine intake exhibited a vertical and rightward shift in the self-administration dose-response function, and were more resistant to extinction from cocaine self-administration, similar to phenotypic changes reported in other models of cocaine addiction. After 3 weeks of withdrawal from cocaine self-administration, high intake rats were subsensitive to the ability of the D 1 agonist SKF 81297 to inhibit cocaine-seeking behavior elicited by cocaine priming, but supersensitive to cocaine seeking triggered by the D 2 agonist quinpirole, when compared to low intake rats. Additionally, high intake rats developed profound increases in locomotor responses to D 2 receptor challenge from early to late withdrawal times, whereas low intake rats developed increased responsiveness to D 1 receptor challenge. In a second experiment, responses to the mixed D 1 /D 2 agonist apomorphine and the NMDA glutamate receptor antagonist MK-801 failed to differ between low and high intake rats. These findings suggest that cocaine addiction is related specifically to differential alterations in functional D 1 and D 2 receptors and their ability to modulate cocaine-seeking behavior.

show abstract

Effects of Cocaine Self-administration on Striatal Dopamine Systems in Rhesus Monkeys Initial and Chronic Exposure

Cited by 192 publications

References 43 publications

Dopamine decreases NMDA currents in the oval bed nucleus of the stria terminalis of cocaine self-administering rats

Dopamine decreases NMDA currents in the oval bed nucleus of the stria terminalis of cocaine self-administering rats

There and Back Again: A Tale of Norepinephrine and Drug Addiction

Addiction-Related Alterations in D1 and D2 Dopamine Receptor Behavioral Responses Following Chronic Cocaine Self-Administration

Contact Info

Product

Resources

About