Chronic cocaine administration increases tyrosine hydroxylase activity in the ventral tegmental area through glutaminergic- and dopaminergic D2-receptor mechanisms

Masserano, Joseph M.; Baker, Ivory; Natsukari, Naoki; Wyatt, Richard Jed

doi:10.1016/0304-3940(96)13047-0

Cited by 44 publications

(13 citation statements)

References 24 publications

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“…Cocaine-induced regulation of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, is well documented in the VTA and dopaminergic terminals of the NAc in studies where cocaine is forcibly administered by repeated bolus intraperitoneal injections (Trulson et al 1987;Beitner-Johnson and Nestler 1991;Sorg et al 1993;Vrana et al 1993;Masserano et al 1996;Todtenkopf et al 2000).…”

Section: Results and Discussion Extinction Training Reverses Cocaine-mentioning

confidence: 99%

Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

Self¹,

Choi²,

Simmons³

et al. 2004

Learn. Mem.

116

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Cocaine produces multiple neuroadaptations with chronic repeated use. Many of these neuroadaptations can be reversed or normalized by extinction training during withdrawal from chronic cocaine self-administration in rats. This article reviews our past and present studies on extinction-induced modulation of the neuroadaptive response to chronic cocaine in the mesolimbic dopamine system, and the role of this modulation in addictive behavior in rats. Extinction training normalizes tyrosine hydroxylase levels in the nucleus accumbens (NAc) shell, an effect that could help ameliorate dysphoria and depression associated with withdrawal from chronic cocaine use. Extinction training also increases levels of GluR1 and GluR2/3 AMPA receptor subunits, while normalizing deficits in NR1 NMDA receptor subunits, in a manner consistent with long-term potentiation of excitatory synapses in the NAc shell. Our results suggest that extinction-induced increases in AMPA and NMDA receptors may restore deficits in cortico-accumbal neurotransmission in the NAc shell and facilitate inhibitory control over cocaine-seeking behavior. Other changes identified by gene expression profiling, including up-regulation in the AMPA receptor aggregating protein Narp, suggest that extinction training induces extensive synaptic reorganization. These studies highlight potential benefits for extinction training procedures in the treatment of drug addiction.

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Section: Results and Discussion Extinction Training Reverses Cocaine-mentioning

confidence: 99%

Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

Self¹,

Choi²,

Simmons³

et al. 2004

Learn. Mem.

116

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“…Coadministration of NMDA or AMPA receptor antagonists, given systemically or directly into the VTA, can prevent the development of stimulantinduced behavioral sensitization (Karler et al, 1989(Karler et al, , 1990(Karler et al, , 1991(Karler et al, , 1994Wolf and Khansa, 1991;Kalivas and Alesdatter, 1993;Stewart and Druhan, 1993;Wolf and Jeziorski, 1993;Cador et al, 1997;Li et al, 1997) and the increases in DA in striatal regions (Jake-Matthews et al, 1997). NMDA antagonists also prevent alternations in the VTA seen early after drug treatment (Wolf et al, 1994;Masserano et al, 1996).…”

Section: Abstract: Bfgf; Amphetamine; Sensitization; Glutamate; Dopamentioning

confidence: 99%

Long-Lasting Induction of Astrocytic Basic Fibroblast Growth Factor by Repeated Injections of Amphetamine: Blockade by Concurrent Treatment with a Glutamate Antagonist

1998

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Repeated administration of stimulant drugs leads to lasting changes in their behavioral and neurochemical effects. These changes are initiated by drug actions in the somatodendritic regions of midbrain dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) and continue to develop for a period of time after termination of drug treatment. Here we show that repeated administration of amphetamine (3.0 mg/kg, i.p.; three injections, once every other day) results in sustained increases in basic fibroblast growth factor immunoreactivity (bFGF-IR) in both VTA and SNc, 200-500% over that seen in saline-treated animals. Increases were observed 24 hr, 72 hr, 1 week and 1 month after the last drug injection. Because glutamate participates in the development of sensitization to stimulant drugs, we assessed the effect of the glutamate antagonist, kynurenic acid (KYN), on amphetamineinduced bFGF-IR. Coadministration of KYN prevented the increases in bFGF-IR in both VTA and SNc assessed 1 week after the amphetamine treatment. No changes in bFGF-IR were observed in the nucleus accumbens or dorsal striatum. bFGF-IR was found to be associated with astrocytes and not with dopaminergic neurons. These findings suggest that sustained enhancement of astrocytic bFGF expression in DA somatodendritic regions is a mechanism whereby stimulant drugs exert enduring effects on midbrain DA function. We hypothesize that increased glutamatergic activity elicited by amphetamine and other stimulant drugs places excessive demands on the functioning of DA neurons recruiting regulatory and neuroprotective processes that lead to enduring changes in DA neuron functioning and connectivity.

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“…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%

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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Chronic cocaine administration increases tyrosine hydroxylase activity in the ventral tegmental area through glutaminergic- and dopaminergic D2-receptor mechanisms

Cited by 44 publications

References 24 publications

Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

Long-Lasting Induction of Astrocytic Basic Fibroblast Growth Factor by Repeated Injections of Amphetamine: Blockade by Concurrent Treatment with a Glutamate Antagonist

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

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