Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.
01 Jul 1988-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 85, Iss: 14, pp 5274-5278
TL;DR: The effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis as mentioned in this paper.
Abstract: The effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis. Drugs abused by humans (e.g., opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine concentrations in both areas, but especially in the accumbens, and elicited hypermotility at low doses. On the other hand, drugs with aversive properties (e.g., agonists of kappa opioid receptors, U-50,488, tifluadom, and bremazocine) reduced dopamine release in the accumbens and in the caudate and elicited hypomotility. Haloperidol, a neuroleptic drug, increased extracellular dopamine concentrations, but this effect was not preferential for the accumbens and was associated with hypomotility and sedation. Drugs not abused by humans [e.g., imipramine (an antidepressant), atropine (an antimuscarinic drug), and diphenhydramine (an antihistamine)] failed to modify synaptic dopamine concentrations. These results provide biochemical evidence for the hypothesis that stimulation of dopamine transmission in the limbic system might be a fundamental property of drugs that are abused.
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Cites background from "Drugs abused by humans preferential..."
...The mesolimbic dopamine system is activated by acute administration of opioids, ethanol, nicotine, and D9-THC (Di Chiara and Imperato, 1988)....
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References
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TL;DR: Recovery of behavioural effects correlated with an increase in the remaining levels of DA in the NAS, and there is evidence that remaining DA levels in theNAS are greater at 90 than at 14 days postoperatively.
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TL;DR: Amphetamine induced vigorous rotational behaviour in rats where the nigrostriatal dopamine system was unilaterally degenerated by an intracerebral injection of 6-hydroxydopamine (6-OH-DA) and evidence was obtained that the amphetamine induced release of DA was dependent upon nerve impulses.
Abstract: Amphetamine induced vigorous rotational behaviour in rats where the nigrostriatal dopamine (DA) system was unilaterally degenerated by an intracerebral injection of 6-hydroxydopamine (6-OH-DA). The rotational behaviour was analysed in a specially designed “rotometer” and found highly reproducable. The intensity of the rotation was proportional to the extent of degeneration in the DA system. The amphetamine site of action was in all probability presynaptic as amphetamine caused a rotation in the opposite direction as compared to the DA receptor stimulating drug apomorphine. Tyrosine hydroxylase inhibition abolished the amphetamine effect, while reserpine potentiated the effect. Evidence was also obtained that the amphetamine induced release of DA was dependent upon nerve impulses. The rotational behaviour reflected the degree of DA receptor stimulation, but changes in the noradrenaline (NA) transmission seemed to modulate the behaviour. Decreased NA transmission after dopamine-β-hydroxylase inhibition increased the rotational behaviour. The unilateral degeneration of the DA system was studied by the changes in posture and movements that occurred during the degeneration. After inhibition of the monoamine oxidase the rats showed a strong rotation beginning on the 23d and ending on the 33d hour after the operation. The rotational behaviour was probably due to degeneration release of DA and equivalent to the degeneration contraction of the nictitating membrane in the peripheral nervous system Amphetamine greatly potentiated the spontaneous degeneration release during this period.
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Journal Article•
TL;DR: It is suggested that different opioid receptors mediate the analgesic effects of morphine and U-50,488, a more selective kappa agonist that causes opioid receptor-mediated sedation, diuresis and corticosteroid elevations.
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803 citations
TL;DR: A method has been developed which permits monkeys to self-administer drug solutions, at will, through indwelling intravenous catheters as mentioned in this paper, and monkeys developed psychological dependence on morphine, codeine, cocaine, d-amphetamine, pentobarbital, ethanol, and caffeine.
Abstract: A method has been developed which permits monkeys to self-administer drug solutions, at will, through indwelling intravenous catheters Psychological dependence on the effects of a drug occurs when a naive monkey voluntarily initiates and maintains self-administration of the drug If, in addition to psychological dependence, the drug also produces psychotoxicity, either directly or upon abrupt withdrawal, it has a potential abuse liability In the present study monkeys developed psychological dependence on morphine, codeine, cocaine, d-amphetamine, pentobarbital, ethanol, and caffeine All of these drugs except caffeine produced psychotoxicity Monkeys did not develop psychological dependence on nalorphine, morphine-nalorphine mixtures, chlorpromazine, mescaline or physiological saline
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TL;DR: The hypothesis that separate neural systems mediate the reinforcing properties of opioid and psychomotor stimulant drugs was tested by examining the role of mesolimbic dopamine neurons in maintaining intravenous heroin and cocaine self-administration and data support the hypothesis that independent neural subtrates are responsible for the reinforcing actions of these two drugs.
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633 citations