Dopaminergic gene expression during amphetamine withdrawal

Persico, Antonio M.; Schindler, Charles W.; Brannock, Michael T.; González, Antonio Morilla; Surratt, Christopher K.; Uhl, George R.

doi:10.1097/00001756-199301000-00010

Cited by 23 publications

(17 citation statements)

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“…With respect to the LC, chronic morphine administration has been shown to increase levels of TH mRNA in one study (Guitart et al, 1990); this effect was not seen in another study (Holmes et al, 1995). Similarly, reports of the effect of chronic cocaine or amphetamine administration on TH mRNA levels in the VTA have been both positive (Hurd et al, 1992;Persico et al, 1993;Vrana et al, 1993) and negative (Sorg et al, 1993), whereas the effect of chronic morphine exposure has not yet been studied. The technical difficulty of reliably detecting changes in mRNA levels in nuclei as small as the LC and VTA may have contributed to these discrepancies.…”

Section: Abstract: Opiate Dependence; Cocaine; Locus Coeruleus; Ventmentioning

confidence: 96%

“…In the ventral tegmental area (V TA), a major midbrain dopaminergic nucleus, levels of TH expression are upregulated in response to chronic administration of several drugs of abuse, including morphine, cocaine, amphetamine, or alcohol (BeitnerJohnson and Nestler, 1991;Hurd et al, 1992;Persico et al, 1993;Sorg et al, 1993;Vrana et al, 1993;Ortiz et al, 1995;Masserano et al, 1996). Such upregulation of TH could contribute to the complex effects that these drugs exert on dopaminergic transmission, which has been implicated in the reinforcing actions of these and most other drugs of abuse (Koob, 1996;Kuhar and Pilotte, 1996;Wise, 1996).…”

Section: Abstract: Opiate Dependence; Cocaine; Locus Coeruleus; Ventmentioning

confidence: 99%

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Regulation of Tyrosine Hydroxylase Promoter Activity by Chronic Morphine in TH9.0-LacZ Transgenic Mice

et al. 1998

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Levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, are known to be upregulated in specific brain regions by chronic administration of drugs of abuse. Chronic morphine administration increases TH levels in the locus coeruleus and ventral tegmental area, whereas chronic cocaine administration increases TH levels in the ventral tegmental area only. While such upregulation of TH has been related to behavioral effects of the drugs, the mechanism underlying these adaptations has remained controversial. To study the possibility that upregulation of TH occurs at the transcriptional level, we investigated the effect of chronic morphine or cocaine treatment on the activity of the TH gene promoter (9.0 kb), coupled to the LacZ reporter gene, in transgenic mice. These TH9.0-LacZ mice have been shown to exhibit correct tissue-specific expression and regulation of the reporter gene. We show here that chronic (but not acute) exposure of the TH9.0-LacZ mice to morphine increases the expression of ␤-galactosidase (which is encoded by the LacZ gene) in the locus coeruleus by twofold compared with shamtreated mice. In contrast, ␤-galactosidase expression in the ventral tegmental area was decreased 20-25% by chronic morphine and unaffected by chronic cocaine administration. Similar results were obtained after analysis of TH mRNA levels in these brain regions by in situ hybridization. These results suggest that chronic morphine upregulates TH expression via transcriptional mechanisms in the locus coeruleus but by posttranscriptional mechanisms in the ventral tegmental area.

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Section: Abstract: Opiate Dependence; Cocaine; Locus Coeruleus; Ventmentioning

confidence: 96%

Section: Abstract: Opiate Dependence; Cocaine; Locus Coeruleus; Ventmentioning

confidence: 99%

Regulation of Tyrosine Hydroxylase Promoter Activity by Chronic Morphine in TH9.0-LacZ Transgenic Mice

et al. 1998

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“…Second, there is a possibility that the METH-induced decrease in VMAT-2 activity [84,85] disrupts the subcellular compartmentation of dopamine, resulting in its enzymatic metabolism and subsequent reduced availability. Also, the expression level of VMAT-2 mRNA was significantly reduced in the midbrain/pons region, including the ventral tegmental area (VTA), substantia nigra pars compacta and locus coeruleus 36 h after AMPH treatment regimen (7.5 mg/kg, i.p., ·2 injections per day for 2 weeks) [86]. Third, the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme responsible for the synthesis of catecholamines, decreased following neurotoxic METH administration (15 mg/kg, s.c., ·4-5 injections every 6 h) in the neostriatum of rats on days 1-30 of withdrawal [87,88].…”

Section: Postmortem Brain Tissue Levels Of Dopamine and Metabolites Amentioning

confidence: 99%

“…The same conclusion as that of Shilling et al [106] was drawn utilizing a similar fixeddose injection regimen (5 mg/kg, i.p., ·one injection per day for 5 days; 3-14 days of drug abstinence) [107]. However, Persico et al [86] observed no change in DAT mRNA expression during AMPH withdrawal (7.5 mg/kg, i.p., ·2 injections per day for 2 weeks; 36 h of drug abstinence) in the midbrain/pons region including the VTA, substantia nigra pars compacta and locus coeruleus. It is likely that that these discrepancies in the changes in DAT mRNA expression can be explained by differences in the type of tissue dissection method and the duration of withdrawal.…”

Section: Datmentioning

confidence: 99%

“…Acute METH administration decreases VMAT-2 activity [84,85], suggesting that METH may disrupt the proper dopamine compartmentation invivo. Persico et al [86] elucidated a possible mechanism underlying METH-induced decrease in VMAT-2 activity, that is, decreased expression level of VMAT-2 mRNA during AMPH withdrawal. This phenomenon was evident in the midbrain.…”

Section: Vmat-2mentioning

confidence: 99%

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Neurochemical Consequences of Dysphoric State During Amphetamine Withdrawal in Animal Models: A Review

Kitanaka

Takemura

2007

Neurochem Res

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Chronic abuse of amphetamines, such as d-amphetamine (AMPH) and d-methamphetamine, results in psychological dependence, a condition in which the drug produces a feeling of satisfaction and a drive that requires periodic or continuous administration of the drug to produce overwhelming pleasure or to avoid discomfort such as dysphoria. The dysphoric state of AMPH withdrawal has been recognized as depressive syndromes, such as anhedonia, depression, anxiety, and social inhibition, in early drug abstinence. Medication for treatment of the dysphoric state is important for AMPH abusers to avoid impulsive self-injurious behavior or acts that are committed with unconscious or uncontrolled suicidal ideation. However, successful treatments for AMPH withdrawal remain elusive, since the exact molecular basis of the expression of dysphoria has not been fully elucidated. This review focuses on the molecular aspects of AMPH withdrawal as indexed by neurochemical parameters under a variety of injection regimens (for example, levels of brain monoamines and their metabolites, and gamma-aminobutyric acid, expression of genes and proteins involved in neuronal activity, and monoamine metabolism and availability) in rodent models which exhibit significant phenotypic features relevant to the syndromes of AMPH withdrawal in humans.

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Spatial and temporal profile of haloperidol‐induced immediate‐early gene expression and phosphoCREB binding in the dorsal and ventral striatum of amphetamine‐sensitized rats

Hsieh

Lin

et al. 2002

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To determine if D(2) dopamine receptor-mediated nuclear signaling is altered during the development of amphetamine sensitization, we examined the expression of immediate-early gene (IEG) products, Fos, Jun, and Fos-related antigen (FRA), in both controls and amphetamine-sensitized rats after a challenge with the D(2) antagonist haloperidol. When chronic saline- or amphetamine (5 mg/kg, i.p. for 14 days)-treated rats were challenged with 2 mg/kg haloperidol at withdrawal day 3 (w3), more 35-kDa FRA was induced in the ventral striatum of the control group than in the amphetamine-treated rats. In contrast, more Jun and 35-kDa FRA were expressed in the ventral striatum of the amphetamine-treated group than in the controls when haloperidol was given at w10. Topographical analyses indicate that the decrease in FRA immunoreactive neuronal density in amphetamine-treated rats at w3 were located in the dorsolateral caudate/putamen and the nucleus accumbens shell and core subregions. Conversely, the increase in Jun-immunoreactive neurons in amphetamine-treated rats at w10 was observed in the dorsolateral caudate/putamen; in the case of the FRAs, the increase was observed in the nucleus accumbens shell. In addition, the time-dependent profile of IEG expression paralleled the activation of an upstream regulator, cAMP-response element binding protein, in the ventral striatum after haloperidol treatment. These neurochemical changes may be associated with behavioral plasticity, since amphetamine-treated rats displayed a lower amount of locomotor activity when exposed to a novel environment at w3, but had recovered at w10. Overall, the current study reveals that there is a distinct temporal and spatial profile of haloperidol-induced IEG expression and/or CREB phosphorylation in amphetamine-treated rats, suggesting that there is a critical transition between the early and late withdrawal periods.

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Dopaminergic gene expression during amphetamine withdrawal

Cited by 23 publications

References 0 publications

Regulation of Tyrosine Hydroxylase Promoter Activity by Chronic Morphine in TH9.0-LacZ Transgenic Mice

Regulation of Tyrosine Hydroxylase Promoter Activity by Chronic Morphine in TH9.0-LacZ Transgenic Mice

Neurochemical Consequences of Dysphoric State During Amphetamine Withdrawal in Animal Models: A Review

Spatial and temporal profile of haloperidol‐induced immediate‐early gene expression and phosphoCREB binding in the dorsal and ventral striatum of amphetamine‐sensitized rats

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