Neurochemical changes in cocaine withdrawal

Kuhar, Michael J.; Pilotte, Nancy S.

doi:10.1016/0165-6147(96)10024-9

Cited by 154 publications

(101 citation statements)

References 41 publications

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“…However, in our earlier PET studies we found that the first day of binge cocaine administration did not alter SCH23390 binding (Tsukada et al 1996). The first day is an acute timepoint at which microdialysis studies from our group and others have shown that single dose or binge cocaine increases extracellular fluid dopamine levels in the striatum to levels that are all significantly higher than dopamine levels in saline treated controls (Maisonneuve and Kreek 1994;Maisonneuve et al 1995;Kuhar and Pilotte 1996;Hammer et al 1997). However, similar microdialysis studies following 14 days of chronic binge cocaine administration showed significantly lower cocaine-induced elevations in extracellular fluid dopamine levels as compared to the levels achieved during the first day of binge cocaine administration (Maisonneuve et al 1995).…”

Section: Discussionmentioning

confidence: 59%

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Sustained Withdrawal Allows Normalization of In Vivo [11C]N-Methylspiperone Dopamine D2 Receptor Binding after Chronic Binge Cocaine A Positron Emission Tomography Study in Rats

Maggos

Tsukada

Kakiuchi

et al. 1998

Neuropsychopharmacology

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Section: Discussionmentioning

confidence: 59%

“…Cocaine has been reported to increase dopamine D 1 and D 2 receptor binding in vitro (Goeders and Kuhar 1987;Unterwald et al 1994;Kuhar and Pilotte 1996;Hammer et al 1997). Cocaine has also been reported to increase both D 1 and D 2 dopamine receptor mRNA levels in rat brain (Laurier et al 1994).…”

Section: Da-r Binding Normalizes Long After Chronic Cocaine 147mentioning

confidence: 99%

Sustained Withdrawal Allows Normalization of In Vivo [11C]N-Methylspiperone Dopamine D2 Receptor Binding after Chronic Binge Cocaine A Positron Emission Tomography Study in Rats

Maggos

Tsukada

Kakiuchi

et al. 1998

Neuropsychopharmacology

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“…In humans, recent evidence from brain-imaging studies suggest a role for dopamine-rich brain regions, including the nucleus accumbens and amygdala, in cocaine craving (Grant et al 1996;Breiter et al 1997;Childress et al 1999). Along this line, considering the particular conditions of this work, it is tempting to speculate that, in addition to previously documented inhibition of mesocorticolimbic activity (Rossetti et al 1992;Kuhar and Pilotte 1996), a decrease in proenkephalin gene expression in the Ce may represent a possible mechanism mediating in cocaine withdrawal states.…”

Section: Discussionmentioning

confidence: 66%

Extinction of Cocaine Self-Administration Produces a Differential Time-Related Regulation of Proenkephalin Gene Expression in Rat Brain

Crespo

Manzanares

Martínez

et al. 2001

Neuropsychopharmacology

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The purpose of this study was to examine the time course effects of extinction of cocaine self-administration behavior on proenkephalin (PENK) gene expression in caudateputamen nucleus (ST), nucleus accumbens (Acc), olfactory tubercle (Tu), piriform cortex (Pir), ventromedial hypothalamic nucleus (VMN), and central amygdala (Ce) as measured by in situ hybridization histochemistry. Seventy-two littermate male Lewis rats were randomly assigned in triads to one of three conditions: (1) contingent intravenous self-administration of 1 mg/kg/injection of cocaine (CONT); (2) noncontingent injections of either 1 mg/kg/injection of cocaine (NONCONT); or (3) saline yoked (SALINE) to the intake of the self-administering subject. The self-administering rats were trained to selfadminister cocaine under a FR5 schedule of reinforcement for a minimum of 3 weeks. After stable baseline levels of drug intake had been reached, saline was substituted for drug. Following this first extinction period, cocaine selfadministration was reinstated for an additional period of 2 weeks. Immediately after cessation of the last session of cocaine self-administration (day 0) and 1-, 5-, and 10-day after the second extinction period, animal brains in eachCocaine abuse and dependence remain major public health and social problems. Cocaine abuse results from a complex interplay of behavioral, pharmacological, and neurobiological determinants. The main pharmacological effect of cocaine is to inhibit the reuptake of monoamines dopamine, norepinephrine, and serotonin at presynaptic terminals. As a consequence of these ac- (Hadfield et al. 1980;Heikkila et al. 1975;Ross and Renyi 1969). The major behavioral effect of cocaine is a psychomotor stimulant action with reinforcing addictive properties. This behavioral effect is produced primarily by inhibition of dopamine uptake, thereby increasing extracellular concentrations of released dopamine (Ritz et al. 1987; for a review see Kuhar et al. 1991;Spanagel and Weiss 1999). However, a recent study using mice lacking dopamine transporter proposed other mechanisms, such as increases in serotonin transmission, may mediate the reinforcing effects of cocaine (Rocha et al. 1998).Several studies have shown that cocaine also affects the expression of opioid peptides and opioid receptors. For example, chronic cocaine administration leads to increases in circulating ␤ -endorphin levels (Moldow and Fischman 1987), striatal preprodynorphin mRNA levels (Hurd et al. 1992;Daunais et al. 1993;Daunais and McGinty, 1995;Spangler et al. 1993Spangler et al. , 1996Spangler et al. , 1997, and striatonigral dynorphin content (Sivam 1989;Smiley et al. 1990) in rats and to decreases in preproenkephalin mRNA levels in rhesus monkeys (Daunais et al. 1997) and humans (Hurd and Herkenham 1993). Repeated administration of cocaine can also regulate the activity of opioid receptors in discrete brain regions of rats. Indeed, it has been shown that 2 weeks of either continuous administration of cocaine via subcutaneously implanted osmotic...

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“…The more rapid clearance of extracellular DA would lead to a decrease in extracellular DA. In previous studies using rodents, repeated administration of cocaine has been shown many times to alter DAT measures, although the nature of these changes has been inconsistent and seems to be influenced by many factors, including mode and pattern of administration, dose, treatment duration, and length of deprivation period (Kuhar and Pilotte, 1996;Chefer and Shippenberg, 2002;Gerrits et al, 2002). In human and non-human primate brains, data concerning changes in DAT binding levels have been conflicting, with increases (Staley et al, 1994;Malison et al, 1998;Letchworth et al, 2001) and decreases (Hurd and Herkenham, 1993) documented.…”

Section: Discussionmentioning

confidence: 99%

“…Repeated administration of cocaine produces changes in many of these measures; however, the magnitude and direction of these changes are inconsistent across studies, probably due to differences in route and pattern of administration, drug dose and length of treatment, and the duration of withdrawal (Kuhar and Pilotte, 1996). The challenge is to evaluate whether such changes are related to the addiction process.…”

Section: Introductionmentioning

confidence: 99%

Reduced Dopamine Terminal Function and Insensitivity to Cocaine Following Cocaine Binge Self-Administration and Deprivation

Mateo

Läck

Morgan

et al. 2005

Neuropsychopharmacol

123

139

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Despite large numbers of studies describing neuroadaptations caused by chronic cocaine exposure, there remains considerable uncertainty as to whether alterations in dopamine (DA) neurotransmission are responsible for progression into an addicted state. Highintake, 24-h access cocaine self-administration (SA, 10 days) followed by an extended (7 days), but not 1 day deprivation period produces an increased motivation to SA cocaine as measured by a progressive ratio protocol. Following binge cocaine SA and deprivation, the status of DA terminals in the nucleus accumbens (NAc) was investigated using microdialysis in freely moving rats and voltammetry in brain slices. At 1 and 7 days following binge cocaine SA, baseline extracellular DA concentrations in the NAc core were decreased by 40 and 55% of control levels, in the 1 and 7 day deprivation groups, respectively. Acute cocaine (1.5 mg/kg, i.v.) administration increased extracellular DA (350%) in the NAc core of naïve animals but failed to significantly increase DA at 1 or 7 days following binge cocaine SA. The shell of the NAc showed a similar lack of effect of cocaine. Analysis of DA terminals in brain slices showed that cocaine was markedly less effective in inhibiting DA uptake at 1 and 7 days of cocaine deprivation (max. effect 40% of control). Electrically stimulated DA release was decreased at 1 day and further decreased at 7 days of deprivation (67 and 49% of control, respectively). The rate of DA uptake was increased (150% of control) following binge SA, irrespective of deprivation period. Finally, presynaptic autoreceptors were subsensitive at both time points, as measured by the ability of quinpirole, a D2-like DA receptor agonist, to inhibit DA release. Thus, the NAc was hypodopaminergic and DA terminals were less sensitive to cocaine following binge cocaine SA and deprivation.

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Neurochemical changes in cocaine withdrawal

Cited by 154 publications

References 41 publications

Sustained Withdrawal Allows Normalization of In Vivo [11C]N-Methylspiperone Dopamine D2 Receptor Binding after Chronic Binge Cocaine A Positron Emission Tomography Study in Rats

Sustained Withdrawal Allows Normalization of In Vivo [11C]N-Methylspiperone Dopamine D2 Receptor Binding after Chronic Binge Cocaine A Positron Emission Tomography Study in Rats

Extinction of Cocaine Self-Administration Produces a Differential Time-Related Regulation of Proenkephalin Gene Expression in Rat Brain

Reduced Dopamine Terminal Function and Insensitivity to Cocaine Following Cocaine Binge Self-Administration and Deprivation

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