Amygdala dopamine levels are markedly elevated after self- but not passive-administration of cocaine

Wilson, Julie M.; Nobrega, JoséN.; Corrigall, William A.; Coen, Kathy; Shannak, Kathleen; Kish, Stephen J.

doi:10.1016/0006-8993(94)90508-8

Cited by 98 publications

(74 citation statements)

References 41 publications

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“…The PET data suggest that the reduction in this subjective response to cocaine by selegiline may involve altering the effect of cocaine on amygdala metabolism and reducing hippocampal metabolic activity. This supposition is consistent with findings from some animal studies (Lyons et al 1996;Madras and Kaufman 1994;Pontieri et al 1995;Stein and Fuller 1993;Imperato et al 1993a;Hsu et al 1996;Wilson et al 1994;Whitelaw et al 1996). These changes seemed to be specific to the limbic region, because they were not present in the thalamus control region.…”

Section: Discussionsupporting

confidence: 92%

“…Animal studies have shown that limbic structures, such as the hippocampus and amygdala, are important in the brain's response to psychostimulants (Stein and Fuller 1993;Imperato et al 1993a;Madras and Kaufman 1994;Pontieri et al 1995;Lyons et al 1996;Hsu et al 1996;Wilson et al 1994;White 1996;Whitelaw et al 1996), human PET studies of cue-induced cocaine craving have shown activation in the medial temporal lobe (Childress et al 1995;Grant et al 1996), and human functional magnetic resonance imaging studies have shown that changes in these regions are associated with subjective effects in cocaine infusion experiments (Breiter et al 1997). In the current study, we focused on limbic structures of the medial temporal lobe (amygdala and hippocampus), and for the purpose of evaluating the specificity of the limbic findings, we also examined the thalamus as a comparison region.…”

Section: To Test the Effect Of Selegiline A Specific Monoamine Oxidamentioning

confidence: 99%

“…These effects consist of increasing dopamine availability by reducing dopamine breakdown through MAO-B inhibition, increasing levels of betaphenylethylamine (another MAO-B specific substrate) resulting in increased synaptic dopamine release and decreasing dopamine reuptake, and enhancing catecholaminergic neuron activity (Paterson et al 1995;Knoll et al 1996) (for review see Gerlach et al 1996). Dopamine agonists with higher abuse potential have also been reported, by addicts who relapsed while being treated with these agents, to reduce the reinforcing subjective experience of euphoria produced by cocaine (Rothman 1995;Rothman et al 1996).Animal studies have shown that limbic structures, such as the hippocampus and amygdala, are important in the brain's response to psychostimulants (Stein and Fuller 1993;Imperato et al 1993a;Madras and Kaufman 1994;Pontieri et al 1995;Lyons et al 1996;Hsu et al 1996;Wilson et al 1994;White 1996;Whitelaw et al 1996), human PET studies of cue-induced cocaine craving have shown activation in the medial temporal lobe (Childress et al 1995;Grant et al 1996), and human functional magnetic resonance imaging studies have shown that changes in these regions are associated with subjective effects in cocaine infusion experiments (Breiter et al 1997). In the current study, we focused on limbic structures of the medial temporal lobe (amygdala and hippocampus), and for the purpose of evaluating the specificity of the limbic findings, we also examined the thalamus as a comparison region.…”

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Selegiline Effects on Cocaine-Induced Changes in Medial Temporal Lobe Metabolism and Subjective Ratings of Euphoria

Bartzokis

Beckson

Newton

et al. 1999

Neuropsychopharmacology

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To test the effect of selegiline, a specific monoamine oxidase-B (MAO-B) inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followedMost screening of medications for the treatment of human addiction is based on animal models. Psychostimulant dependence lacks the clear physiologic dependence syndrome seen in opiate and alcohol dependence; therefore, animal models of psychostimulant dependence evaluate behavioral parameters. However, the N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 6 Selegiline Effects on Brain Metabolism and Euphoria 583 lack of subjective responses in animal models and the vast differences between the behavior of human addicts and animal models of addiction, make it desirable to screen candidate medications based upon their ability to change the subjective experiences of psychostimulant addicts (Satel et al. 1995;Berger et al. 1996).One aspect of addiction where a pharmacological intervention might prove effective is the euphoric subjective experience to drugs that reinforces drug use behaviors (O'Brien et al. 1996;Volpicelli et al. 1995). The effects of cocaine infusion on regional brain function have been studied in only two prior studies of cocaine addicts. In the first of these, 40-mg cocaine infusion reduced cerebral glucose metabolism globally, as measured with [F-18] fluorodeoxyglucose and positron emission tomography (PET) (London et al. 1990). A subsequent single-photon emission tomography (SPECT) study of cerebral perfusion showed that, after normalizing the data to counts in the cerebellum, 48 mg of cocaine decreased blood flow in frontal cortical and basal ganglia regions (Pearson et al. 1993).Although our understanding of the euphoria or "high" produced by cocaine in humans is limited, animal studies indicate that mesolimbic dopamine neurotransmission and the limbic system play major roles in cocaineinduced reinforcement (for reviews see Wise 1996;White 1996). Effects on mesocorticolimbic dopaminergic pathways are believed to be critical to the development of the dependence syndrome (Koob and Weiss 1992;Schultz et al. 1993). Efforts to develop a treatment for cocaine abuse have focused on dopaminergic systems, with the assumption that effective medications must substitute for, normalize, or block the effects of cocaine on this system (Blaine and Ling 1992;Tutton and Crayton 1993). Selegiline was chosen for this protocol because of its low abuse potential (Schneider et al. 1994), its safety when given in conjunction with cocaine infusion (Haberny et al. 1995), and its indirect dopamine agonist effects. These effects consist of increasing dopamine availability by reducing dopamine breakdown through MAO-B inhibition, increasing levels of betaphenylethylamine (another MAO-B specific substrate) resulting in increased synaptic ...

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Section: Discussionsupporting

confidence: 92%

Section: To Test the Effect Of Selegiline A Specific Monoamine Oxidamentioning

confidence: 99%

mentioning

confidence: 99%

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Selegiline Effects on Cocaine-Induced Changes in Medial Temporal Lobe Metabolism and Subjective Ratings of Euphoria

Bartzokis

Beckson

Newton

et al. 1999

Neuropsychopharmacology

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“…brain and behavior (Wilson et al, 1994;Dworkin et al, 1995;Jacobs et al, 2003). In addition, it is not surprising that different results are obtained in a classical conditioning CPP procedure and an operant self-administration procedure; there is evidence in the literature for both similarities and differences in the anatomical substrates of the reinforcing effects of drugs, as measured in the two procedures (Bardo and Bevins, 2000).…”

Section: Nicotine Self-administration In Adolescent and Adult Ratsmentioning

confidence: 99%

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

Shram

Funk

et al. 2007

Neuropsychopharmacol

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Initiation of smoking behavior typically occurs during adolescence and rarely occurs during adulthood. Despite this epidemiological evidence, relatively little is known about possible neurobiological differences in the response to nicotine in adolescents that might make them more vulnerable to nicotine addiction. In the current study, we assessed nicotine self-administration under fixed ratio (FR) and progressive ratio (PR) reinforcement schedules in adolescent (postnatal day (P) 33-35) and adult (P91-94) rats. We then assessed extinction and reinstatement of nicotine seeking in adulthood in rats that initiated nicotine self-administration during either adolescence or adulthood. Nicotine self-administration (0.03 mg/kg/infusion, i.v.) was higher in adult rats than in adolescent rats under FR5 and PR reinforcement schedules; no age differences in nicotine self-administration were observed under FR1 or FR2 reinforcement schedules. In contrast, saccharin self-administration under FR5 and PR reinforcement schedules was similar in both age groups, potentially ruling out age differences in general performance. Rats that initiated nicotine self-administration as adults demonstrated a greater resistance to extinction of nicotine taking behavior when saline was substituted for nicotine than rats that initiated self-administration as adolescents. Reinstatement of nicotine seeking following nicotine priming injections (0.075, 0.15, 0.3 mg/kg, s.c.) was independent of the age of onset of nicotine self-administration. The present data from established rat models of drug self-administration and drug relapse suggest that nicotine is less reinforcing in adolescent compared with adult rats and that processes other than the reinforcing effects of nicotine may be involved in the greater susceptibility to smoking during the adolescent developmental stage.

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“…In this respect, the majority of studies investigating cocaine-induced cellular neuroadaptations use repeated noncontingent administration of this drug; whereas, fewer studies employ drug selfadministration. However, long-term neuroadaptations to chronic cocaine administration could arise not only from the pharmacological actions of cocaine on neurotransmitter systems but also by an interaction between this pharmacological action and the animal's environment (Dworkin et al 1992(Dworkin et al , 1995Wilson et al 1994;Hemby et al 1997). Indeed, it has been suggested that in humans the classical conditioning of the pharmacological actions of cocaine with environmental stimuli plays an important role in long-term addictive potential of this drug and in the liability to relapse in recovering cocaine addicts (Ehrman et al 1992).…”

Section: The Purpose Of This Study Was To Examine the Time Course Effmentioning

confidence: 99%

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...

show abstract

Amygdala dopamine levels are markedly elevated after self- but not passive-administration of cocaine

Cited by 98 publications

References 41 publications

Selegiline Effects on Cocaine-Induced Changes in Medial Temporal Lobe Metabolism and Subjective Ratings of Euphoria

Selegiline Effects on Cocaine-Induced Changes in Medial Temporal Lobe Metabolism and Subjective Ratings of Euphoria

Nicotine Self-Administration, Extinction Responding and Reinstatement in Adolescent and Adult Male Rats: Evidence Against a Biological Vulnerability to Nicotine Addiction during Adolescence

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

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