Electrophysiological evidence for excitation of rat ventral tegmental area dopamine neurons by morphine

doi:10.1016/0306-4522(84)90048-4

Neuroscience

Volume 11, Issue 3, March 1984, Pages 617-625

https://doi.org/10.1016/0306-4522(84)90048-4 Get rights and content

Abstract

A considerable body of evidence indicates that opiates have an important influence on midbrain dopaminergic neurons. However, little data exist concerning the effects of opiates on the activity of single dopaminergic neurons, particularly the dopaminergic neurons of the ventral tegmental area. Firing rates of mesencephalic dopaminergic neurons were recorded extracellularly, and the effects of morphine, administered systemically or applied locally onto dopaminergic cells, were tested in paralyzed, unanesthetized or chloral hydrate anesthetized rats. In general, dopaminergic neurons were excited by both systemically and locally applied morphine. When mesencephalic dopaminergic neurons were subdivided into substantia nigra zona compacta (A9) and ventral tegmental area (A10) neurons, A10 neurons were excited 2–3 times more than A9 neurons by systemic morphine. Systemic administration of the specific opiate antagonist, naloxone, in large part reversed the effects of morphine. Microiontophoretic or micropressure ejection of morphine caused an apparent depolarization-induced excitation of both A10 and A9 dopaminergic neurons.

These results provide direct evidence that morphine increases impulse flow of A10 dopaminergic neurons, which are known to be involved in locomotor stimulant and positive reinforcement effects of opiates.

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Citation Excerpt :
These morphine effects are consistent with a large number of studies in rodents that have shown that drugs which have pro-dopamine effects such as amphetamine (Robinson, 1984; Mazurski and Beninger, 1987; Anagnostaras et al., 2002; Singer et al., 2014), cocaine (Carey and Gui, 1998; Horger et al., 1999; Zavala et al., 2000; Carey and Damianopoulos, 2006; Todtenkopf and Carlezon, 2006) and apomorphine (Mattingly and Gotsick, 1989; Damianopoulos and Carey, 1993; Võikar et al., 1999; Keller et al., 2002; Bloise et al., 2007; de Matos et al., 2010; Santos et al., 2017) induce locomotor hyper-activity effects with repeated drug/environment pairings. In line with the presumed important role of dopamine in conditioning, morphine has been shown to increase dopamine activity in the ventral tegmental area (VTA) via the disinhibition of dopaminergic neurons in the VTA by the inhibitory action of morphine at the mu-opioid receptor on GABA inhibitory neurons (van der Kooy et al., 1982; Matthews and German, 1984; Johnson and North, 1992; Brown et al., 2012; Tan et al., 2012). In that the VTA is implicated in reward and that reward effects facilitate associative processes; it is not surprising that morphine stimulant effects are context specific (Leite Júnior et al., 2019; de Mello Bastos et al., 2020).
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^*: Present address: Department of Anatomy, Texas A&M School of Medicine, College Station, TX 77843, U.S.A.

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Electrophysiological evidence for excitation of rat ventral tegmental area dopamine neurons by morphine

Abstract

Life Sci.

J. Neuropharmac.

Neuropharmacology

Brain Res.

Life Sci.

Brain Res.

Neurosci. Letts

Neurosci. Letts

Life Sci.

Eur. J. Pharmac.

Brain Res.

Brain Res.

Eur. J. Pharmac.

Prog. Neuropsychopharmac.

Morphine differentially alters synthesis and turnover of dopamine in central neuronal systems

J. Neural. Trans.

Time-dose relationships for locomotor activity effects of morphine after acute or repeated treatment

Br. J. Pharmac.

Electrophysiological effects of opiates and opioid peptides

Stimulant effects of enkephalin microinjection into the dopaminergic A10 area

Nature, Lond.

Comparison of effects of l-dopa, amphetamine and apomorphine on the firing rate of rat dopaminergic neurons

Nature, New Biol.

Acute and chronic haloperidol treatment: comparison of effects on nigral dopaminergic activity

Life Sci.

Dopaminergic neurons: effects of antipsychotic drugs and amphetamine on single cell activity

J. Pharmac. exp. The´r.