Electrophysiological Pharmacology of Mesencephalic Dopaminergic Neurons

Diana, Marco; Tepper, James M.

doi:10.1007/978-3-662-06765-9_1

Cited by 21 publications

(18 citation statements)

References 336 publications

(412 reference statements)

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“…Furthermore, the results presented here suggest that the enhancement of dopaminergic transmission after ethanol administration (Gessa et al, 1985;Brodie et al, 1990) might be at least partially mediated by acetaldehyde. Accordingly, acetaldehyde administered alone, like ethanol, readily and dosedependently increased the firing rate, spikes/burst, and burst firing of DA-containing neurons of the VTA, a brain region that is known to be involved in the motivational properties of drugs of abuse in general, including ethanol (see Pulvirenti and Diana, 2001;Diana and Tepper, 2002 for recent reviews). In addition, acetaldehyde stimulated the electrophysiological activity of VTA-DA neurons in animals in which ethanol metabolism was pharmacologically blocked by the ADH-inhibitor 4-MP, whereas this ethanol property was significantly reduced under this condition.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, ethanol withdrawal decreases dopaminergic neuronal activity in rats in vivo (Diana et al, 1993) and mice in vitro (Bailey et al, 1998), and reduces DA extracellular concentrations in the nucleus accumbens (Rossetti et al, 1992;Diana et al, 1993;Weiss et al, 1996). All these studies have suggested that both positive (reinforcing) and negative (dysphoriant) properties induced by acute ethanol and its withdrawal, respectively, are mediated, at least partially, by increments and decrements of DA neurons activity projecting to the nucleus accumbens (Diana, 1996(Diana, , 1998Pulvirenti and Diana, 2001;Diana and Tepper, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, at least some of the motivational properties of ethanol are thought to be mediated by the mesolimbic dopamine (DA) system, whose cell bodies are located in the ventro tegmental area (VTA) of the midbrain (see Diana and Tepper, 2002, for a recent review). Accordingly, acute ethanol administration increases the electrophysiological activity of these neurons in vivo (Gessa et al, 1985) and in vitro (Brodie et al, 1990), and augments DA microdialysate concentrations in terminal areas (Imperato and Di Chiara, 1986) of freely behaving rats.…”

Section: Introductionmentioning

confidence: 99%

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Acetaldehyde Increases Dopaminergic Neuronal Activity in the VTA

Foddai

Dosia

Spiga

et al. 2003

Neuropsychopharmacol

156

137

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Acetaldehyde is the first and principal metabolite of ethanol administered systemically. To its rise in blood, after administration of disulfiram, is ascribed the aversive reaction that should discourage alcoholics from drinking. In the present study, we sought to determine the effect of acetaldehyde on the electrophysiological properties of dopamine (DA)-containing neurons in the ventro tegmental area (VTA) of rats in vivo. Intravenous (i.v.) administration of acetaldehyde (5-40 mg/kg) readily and dose-dependently increased the firing rate, spikes/burst, and burst firing of VTA neurons. Ethanol (250-1000 mg/kg/i.v.) administration produced similar increments in electrophysiological parameters. In addition, a second group of rats was pretreated with the alcohol-dehydrogenase inhibitor 4-methylpyrazole (90 mg/kg) intraperitoneally (i.p.), and ethanol and acetaldehyde were administered i.v. at the same doses, 48 h later. In this group, ethanol effects were drastically reduced and the firing rate, spikes/burst, and burst firing were not significantly altered. In contrast, acetaldehyde fully retained its capacity to stimulate electrophysiological indices. The results indicate that acetaldehyde produces electrophysiological actions on VTA neurons in vivo, similar to those produced by ethanol, and significantly participate in ethanol-induced increment in DA neuronal activity. These results also suggest that acetaldehyde, by increasing DA neuronal activity in the VTA, may significantly contribute to the centrally mediated positive motivational properties of ethanol, which would oppose the well-known peripherally originating aversive properties.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acetaldehyde Increases Dopaminergic Neuronal Activity in the VTA

Foddai

Dosia

Spiga

et al. 2003

Neuropsychopharmacol

156

137

View full text Add to dashboard Cite

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“…Dopaminergic mechanisms of the striatum are involved in motor coordination and disorders such as schizophrenia, Tourette's syndrome, drug addiction, and Parkinson disease (Graybiel et al, 1994;Breiter et al, 1997;Lang and Lozano, 1998;Kalivas and Nakamura, 1999;D'Aquila et al, 2000;Nicola et al, 2000;Grace, 2000;Diana and Tepper, 2002). Dopamine (DA) also has complex participation in the processes associated with reinforcing behaviors that lead to reward (Schultz et al, 1997;Spanagel and Weiss, 1999;Berke and Hyman, 2000;Wise, 2000;.…”

Section: Introductionmentioning

confidence: 99%

Cholinergic interneuron characteristics and nicotinic properties in the striatum

2002

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ABSTRACT:The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.

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“…The electrophysiological properties of dopaminergic neurons have been studied in detail, both in vivo and in vitro (for recent review, see Diana and Tepper, 2002). Almost all nigrostriatal dopaminergic neurons fire spontaneously in vivo (Tepper et al, 1984;Dai and Tepper, 1998; but see Chiodo, 1988;Floresco et al, 2003) at relatively slow rates averaging between 4 and 5 spikes/s (Bunney et al, 1973;Deniau et al, 1978;Guyenet and Aghajanian, 1978;Bunney, 1979;Grace and Bunney, 1983).…”

Section: Introductionmentioning

confidence: 99%