A dopaminergic-glutamatergic basis for the action of amphetamine and cocaine

Karler, Ralph; Calder, Larry D.; Thai, Lam H.; Bedingfield, J.Brent

doi:10.1016/s0006-8993(09)90003-8

Cited by 79 publications

(26 citation statements)

References 20 publications

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“…These results have broad implications for the cellular basis of neuronal adaptation during motor learning and, in light of results of previous research on the nucleus accumbens (Smith-Roe and Kelley, 2000), provide evidence for parallel cellular mechanisms within discrete regions of the proposed neural network mediating such learning. Furthermore, because there is mounting evidence for dopamine-NMDA interactions in behavioral measures associated with chronic drug administration (Karler et al, 1994;Wolf et al, 1994;Kalivas, 1995;Sonsalla, 1995;Wolf and Xue, 1998;Vanderschuren and Kalivas, 2000), these results may be important for current theories of drug addiction, a physiological process that may involve the same neural substrates as appetitive instrumental learning (Robinson and Berridge, 1993;Robinson and Berridge, 2001).…”

Section: Discussionmentioning

confidence: 99%

Appetitive Instrumental Learning Requires Coincident Activation of NMDA and Dopamine D1 Receptors within the Medial Prefrontal Cortex

Baldwin¹,

2002

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Through its complex role in cognition, memory, and emotion, the mammalian prefrontal cortex is thought to contribute to the organization of adaptive behavioral actions. In the present studies we examined the role of dopaminergic D1 and glutamatergic NMDA receptors within the prefrontal cortex of the rat during the development of adaptive instrumental learning. Hungry rats with bilateral indwelling cannulas aimed at the medial prefrontal cortex were trained to lever-press for food. Infusion of the selective D1 antagonist SCH-23390 (0.15, 0.3, 3.0 nmol) dosedependently impaired acquisition of this behavior. Higher doses also impaired expression of this task. Co-infusion of the lowest dose of SCH 23390 with a low dose of the NMDA antagonist AP-5 (0.5 nmol), each of which had no effect on learning when infused alone, potently reduced the ability to acquire the response. Inhibition of intracellular protein kinase A with the selective PKA inhibitor Rp-cAMPS also disrupted acquisition, suggesting that PKA is an intracellular substrate for a D1-NMDA receptor interaction. In control experiments, drug infusions that impaired learning did not affect food intake or locomotion, suggesting a specific effect on learning. We hypothesize that coincident detection of D1-NMDA receptor activation and its transcriptional consequences, within multiple sites of a distributed corticostriatal network, may represent a conserved molecular mechanism for instrumental learning.

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Section: Discussionmentioning

confidence: 99%

Appetitive Instrumental Learning Requires Coincident Activation of NMDA and Dopamine D1 Receptors within the Medial Prefrontal Cortex

Baldwin¹,

2002

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“…Furthermore, studies have shown that glutamate plays an important role in the initiation of the changes accompanying sensitized responding. 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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“…Recent evidence suggests that certain stimulant effects are mediated by glutamate. For example, studies have shown that the locomotor stimulatory properties of cocaine and amphetamine (Karler et al, 1992(Karler et al, , 1994Pulvirenti et al, 1994) and the dopamine release stimulatory properties of cocaine (Moghaddam and Bolinao, 1994;Pap and Bradberry, 1995) can be blocked by glutamatergic antagonists. Furthermore, an acute dose of cocaine has been shown to increase glutamate turnover and release in the nucleus accumbens (Robinson et al, 1994;Smith et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Cocaine and amphetamine preferentially stimulate glutamate release in the limbic system: Studies on the involvement of dopamine

Reid

Hsu

Berger

1997

Synapse

188

109

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The effects of cocaine and d-amphetamine on extracellular glutamate and aspartate levels in the nucleus accumbens, prefrontal cortex, and striatum were studied by in vivo microdialysis in awake, freely moving rats. In the nucleus accumbens, glutamate levels were stimulated by cocaine (15-30 mg/kg, i.p.), GBR 12909 (15 mg/kg, i.p.), and d-amphetamine (2 mg/kg, i.p.), while aspartate levels were not affected. The increase in nucleus accumbens glutamate levels following cocaine (30 mg/kg) was calcium-dependent and was blocked by pretreatment with dopamine antagonists; haloperidol (0.2 mg/kg, i.p.), SCH 23390 (0.02 mg/kg, i.p.), and raclopride (1 mg/kg, i.p.), as well as local 6-OHDA lesions of the nucleus accumbens. In the prefrontal cortex, glutamate levels were stimulated by both cocaine (15-30 mg/kg, i.p.) and d-amphetamine (2 mg/kg, i.p.), while aspartate levels were moderately stimulated by d-amphetamine only. The increase in prefrontal cortex glutamate levels following cocaine (30 mg/kg) was calcium-dependent and was blocked by pretreatment with SCH 23390 (0.02 mg/kg, i.p.), but not haloperidol (0.2 mg/kg, i.p.) or raclopride (1 mg/kg, i.p.). In the striatum, glutamate and aspartate levels were not affected by either cocaine (15-30 mg/kg, i.p.) or d-amphetamine (2 mg/kg, i.p.). These findings demonstrate that stimulants enhance glutamate release in limbic brain structures, nucleus accumbens, and prefrontal cortex, but not extrapyamidal brain structures, striatum. Furthermore, the increase in glutamate release in the nucleus accumbens may be mediated by dopamine.

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A dopaminergic-glutamatergic basis for the action of amphetamine and cocaine

Cited by 79 publications

References 20 publications

Appetitive Instrumental Learning Requires Coincident Activation of NMDA and Dopamine D1 Receptors within the Medial Prefrontal Cortex

Appetitive Instrumental Learning Requires Coincident Activation of NMDA and Dopamine D1 Receptors within the Medial Prefrontal Cortex

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

Cocaine and amphetamine preferentially stimulate glutamate release in the limbic system: Studies on the involvement of dopamine

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