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Proc Natl Acad Sci U S A. Jul 1988; 85(14): 5274–5278.
PMCID: PMC281732

Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.

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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  • Deneau G, Yanagita T, Seevers MH. Self-administration of psychoactive substances by the monkey. Psychopharmacologia. 1969;16(1):30–48. [PubMed]
  • Wise RA, Bozarth MA. Action of drugs of abuse on brain reward systems: an update with specific attention to opiates. Pharmacol Biochem Behav. 1982 Aug;17(2):239–243. [PubMed]
  • Bozarth MA, Wise RA. Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci. 1981 Feb 2;28(5):551–555. [PubMed]
  • Spyraki C, Fibiger HC, Phillips AG. Cocaine-induced place preference conditioning: lack of effects of neuroleptics and 6-hydroxydopamine lesions. Brain Res. 1982 Dec 16;253(1-2):195–203. [PubMed]
  • Pettit HO, Ettenberg A, Bloom FE, Koob GF. Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology (Berl) 1984;84(2):167–173. [PubMed]
  • Mackey WB, van der Kooy D. Neuroleptics block the positive reinforcing effects of amphetamine but not of morphine as measured by place conditioning. Pharmacol Biochem Behav. 1985 Jan;22(1):101–105. [PubMed]
  • Yokel RA, Wise RA. Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacology (Berl) 1976 Aug 17;48(3):311–318. [PubMed]
  • Spyraki C, Fibiger HC, Phillips AG. Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res. 1982 Dec 16;253(1-2):185–193. [PubMed]
  • Zetterström T, Sharp T, Marsden CA, Ungerstedt U. In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine. J Neurochem. 1983 Dec;41(6):1769–1773. [PubMed]
  • Imperato A, Di Chiara G. Trans-striatal dialysis coupled to reverse phase high performance liquid chromatography with electrochemical detection: a new method for the study of the in vivo release of endogenous dopamine and metabolites. J Neurosci. 1984 Apr;4(4):966–977. [PubMed]
  • Imperato A, Di Chiara G. Dopamine release and metabolism in awake rats after systemic neuroleptics as studied by trans-striatal dialysis. J Neurosci. 1985 Feb;5(2):297–306. [PubMed]
  • Ungerstedt U. Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol Scand Suppl. 1971;367:49–68. [PubMed]
  • Mucha RF, Herz A. Preference conditioning produced by opioid active and inactive isomers of levorphanol and morphine in rat. Life Sci. 1986 Jan 20;38(3):241–249. [PubMed]
  • Portoghese PS, Larson DL, Sayre LM, Fries DS, Takemori AE. A novel opioid receptor site directed alkylating agent with irreversible narcotic antagonistic and reversible agonistic activities. J Med Chem. 1980 Mar;23(3):233–234. [PubMed]
  • Mucha RF, Herz A. Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology (Berl) 1985;86(3):274–280. [PubMed]
  • Tang AH, Collins RJ. Behavioral effects of a novel kappa opioid analgesic, U-50488, in rats and rhesus monkeys. Psychopharmacology (Berl) 1985;85(3):309–314. [PubMed]
  • Vonvoigtlander PF, Lahti RA, Ludens JH. U-50,488: a selective and structurally novel non-Mu (kappa) opioid agonist. J Pharmacol Exp Ther. 1983 Jan;224(1):7–12. [PubMed]
  • Römer D, Büscher H, Hill RC, Maurer R, Petcher TJ, Welle HB, Bakel HC, Akkerman AM. Bremazocine: a potent, long-acting opiate kappa-agonist. Life Sci. 1980 Sep 15;27(11):971–978. [PubMed]
  • Römer D, Büscher HH, Hill RC, Maurer R, Petcher TJ, Zeugner H, Benson W, Finner E, Milkowski W, Thies PW. An opioid benzodiazepine. Nature. 1982 Aug 19;298(5876):759–760. [PubMed]
  • Reid LD, Hunter GA, Beaman CM, Hubbell CL. Toward understanding ethanol's capacity to be reinforcing: a conditioned place preference following injections of ethanol. Pharmacol Biochem Behav. 1985 Mar;22(3):483–487. [PubMed]
  • Stewart RB, Grupp LA. Some determinants of the motivational properties of ethanol in the rat: concurrent administration of food or social stimuli. Psychopharmacology (Berl) 1985;87(1):43–50. [PubMed]
  • Fudala PJ, Teoh KW, Iwamoto ET. Pharmacologic characterization of nicotine-induced conditioned place preference. Pharmacol Biochem Behav. 1985 Feb;22(2):237–241. [PubMed]
  • Spyraki C, Fibiger HC, Phillips AG. Attenuation by haloperidol of place preference conditioning using food reinforcement. Psychopharmacology (Berl) 1982;77(4):379–382. [PubMed]
  • Matthews RT, German DC. Electrophysiological evidence for excitation of rat ventral tegmental area dopamine neurons by morphine. Neuroscience. 1984 Mar;11(3):617–625. [PubMed]
  • Mereu G, Fadda F, Gessa GL. Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats. Brain Res. 1984 Jan 30;292(1):63–69. [PubMed]
  • Clarke PB, Hommer DW, Pert A, Skirboll LR. Electrophysiological actions of nicotine on substantia nigra single units. Br J Pharmacol. 1985 Aug;85(4):827–835. [PMC free article] [PubMed]
  • Kelly PH, Seviour PW, Iversen SD. Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 1975 Sep 5;94(3):507–522. [PubMed]

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