Dopamine-dependent Hyperactivity in the Rat Following Manipulation of GABA Mechanisms in the Region of the Nucleus Accumbens

Overview

Journal J Neural Transm

Specialties Neurology
Physiology

Date 1979 Jan 1

PMID 112217

Citations 9

Authors

C J Pycock

R W Horton

Affiliations

Soon will be listed here.

Abstract

The effect of manipulation of GABA mechanisms in the region of the nucleus accumbens on dopamine-dependent locomotor hyperactivity in the rat has been studied. Two models of hyperactivity were used: (1) the injection of dopamine into the region of the nucleus accumbens in nialamide-pretreated animals and (2) the systemic administration of d-amphetamine. Both GABA and the GABA agonist 3-aminopropane sulphonic acid (3-APS) depressed hyperactivity in a dose-related manner. High concentrations of GABA (greater than 100 micrograms) were required to produce a significant effect and the response was short-lived possibly reflecting the efficient GABA inactivating mechanisms. 3-APS proved to be approximately 10 times more potent as compared to GABA in the dopamine-accumbens hyperactivity model. Conversely GABA receptor antagonism with low doses of either picrotoxin or bicuculline enhanced the mild locomotor response induced by a low dose of dopamine injected into the nucleus accumbens. However such results were difficult to evaluate fairly as higher doses of the GABA antagonists resulted in varying degrees of generalized seizures. Blockade of GABA uptake systems with cis-1, 3-aminocyclohexane carboxylic acid (ACHC), nipecotic acid or beta-alanine within the region of the nucleus accumbens produced dose-related depression of dopamine-dependent hyperactivity in both models. GABA uptake blockade (nipecotic acid) significantly enhanced the GABA-mediated depression of hyperactivity induced by bilateral injection of dopamine into the nucleus accumbens. The results demonstrate an inhibitory action of GABA and drugs facilitating GABA-ergic transmission on dopamine-dependent hyperactivity in the rat. Although open to criticisms of not being able to distinguish between true GABA effects and the results of non-specific neuronal depression the hyperactivity model underlines the potency of the GABA uptake blocking compounds and their possible potential for future clinical use.

Citing Articles

Disinhibition of the Nucleus Accumbens Leads to Macro-Scale Hyperactivity Consisting of Micro-Scale Behavioral Segments Encoded by Striatal Activity.

Yael D, Tahary O, Gurovich B, Belelovsky K, Bar-Gad I J Neurosci. 2019; 39(30):5897-5909.

PMID: 31126998 PMC: 6650982. DOI: 10.1523/JNEUROSCI.3120-18.2019.

Autism-linked dopamine transporter mutation alters striatal dopamine neurotransmission and dopamine-dependent behaviors.

DiCarlo G, Aguilar J, Matthies H, Harrison F, Bundschuh K, West A J Clin Invest. 2019; 129(8):3407-3419.

PMID: 31094705 PMC: 6668686. DOI: 10.1172/JCI127411.

Elevated striatal γ-aminobutyric acid in youth with major depressive disorder.

Bradley K, Alonso C, Mehra L, Xu J, Gabbay V Prog Neuropsychopharmacol Biol Psychiatry. 2018; 86:203-210.

PMID: 29890194 PMC: 6563904. DOI: 10.1016/j.pnpbp.2018.06.004.

Activation of neurotensin receptor type 1 attenuates locomotor activity.

Vadnie C, Hinton D, Choi S, Choi Y, Ruby C, Oliveros A Neuropharmacology. 2014; 85:482-92.

PMID: 24929110 PMC: 4107019. DOI: 10.1016/j.neuropharm.2014.05.046.

Is the dopaminergic system involved in the central effects of nicotine in mice?.

Damaj M, Martin B Psychopharmacology (Berl). 1993; 111(1):106-8.

PMID: 7870924 DOI: 10.1007/BF02257415.

References

Huot S, Lippert B, Palfreyman M, Schechter P . Inhibition of dopaminergic activity in the extrapyramidal and limbic systems by gamma-acetylenic GABA [proceedings]. Br J Pharmacol. 1977; 60(2):264P-265P. PMC: 1667452. View

Green A, Tordoff A, Bloomfield M . Elevation of brain GABA concentrations with amino-oxyacetic acid; effect on the hyperactivity syndrome produced by increased 5-hydroxytryptamine synthesis in rats. J Neural Transm. 1976; 39(1-2):103-12. DOI: 10.1007/BF01248769. View

Johnston G, Krogsgaard-Larsen P, Stephanson A, Twitchin B . Inhibition of the uptake of GABA and related amino acids in rat brain slices by the optical isomers of nipecotic acid. J Neurochem. 1976; 26(5):1029-32. DOI: 10.1111/j.1471-4159.1976.tb06488.x. View

Scheel-Kruger J, Cools A, Honig W . Muscimol antagonizes the ergometrine-induced locomotor activity in nucleus accumbens: evidence for a GABA--dopaminergic interaction. Eur J Pharmacol. 1977; 42(3):311-3. DOI: 10.1016/0014-2999(77)90300-4. View

Curtis D, Watkins J . Analogues of glutamic and gamma-amino-n-butyric acids having potent actions on mammalian neurones. Nature. 1961; 191:1010-1. DOI: 10.1038/1911010a0. View

Stoof J, Mulder A . Increased dopamine release from rat striatal slices by inhibitors of GABA-aminotransferase. Eur J Pharmacol. 1977; 46(2):177-80. DOI: 10.1016/0014-2999(77)90254-0. View

BIRD E, Iversen L . Huntington's chorea. Post-mortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia. Brain. 1974; 97(3):457-72. DOI: 10.1093/brain/97.1.457. View

Iversen L, Kelly J . Uptake and metabolism of gamma-aminobutyric acid by neurones and glial cells. Biochem Pharmacol. 1975; 24(9):933-8. DOI: 10.1016/0006-2952(75)90422-0. View

Kerwin R, Pycock C . Baclofen (beta-p-chlorophenyl-gamma-aminobutyric acid) enhances [3H]gamma-aminobutyric acid (3H-GABA) release from rat globus pallidus in vitro. J Pharm Pharmacol. 1978; 30(10):622-7. DOI: 10.1111/j.2042-7158.1978.tb13343.x. View

10.

Waddington J, Cross A . Neurochemical changes following kainic acid lesions of the nucleus accumbens: implications for a GABAergic accumbal-ventral tegmental pathway. Life Sci. 1978; 22(11):1011-4. DOI: 10.1016/0024-3205(78)90367-3. View

11.

Balcom G, Lenox R, Meyerhoff J . Regional gamma-aminobutyric acid levels in rat brain determined after microwave fixation. J Neurochem. 1975; 24(4):609-13. View

12.

BIRD E, Spokes E, Barnes J, Mackay A, Iversen L, Shepherd M . Increased brain dopamine and reduced glutamic acid decarboxylase and choline acetyl transferase activity in schizophrenia and related psychoses. Lancet. 1977; 2(8049):1157-8. DOI: 10.1016/s0140-6736(77)91542-2. View

13.

Kelly P, Seviour P, Iversen S . Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 1975; 94(3):507-22. DOI: 10.1016/0006-8993(75)90233-4. View

14.

Creese I, Iversen S . The role of forebrain dopamine systems in amphetamine induced stereotyped behavior in the rat. Psychopharmacologia. 1974; 39(4):345-57. DOI: 10.1007/BF00422974. View

15.

McGeer P, McGeer E, Hattori T . Dopamine-acetylcholine-GABA neuronal linkages in the extrapyramidal and limbic systems. Adv Biochem Psychopharmacol. 1977; 16:397-402. View

16.

Krogsgaard-Larsen P, Johnston G, Curtis D, Game C, McCulloch R . Structure and biological activity of a series of conformationally restricted analogues of GABA. J Neurochem. 1975; 25(6):803-9. DOI: 10.1111/j.1471-4159.1975.tb04411.x. View

17.

Giorguieff M, Kemel M, Glowinski J, Besson M . Stimulation of dopamine release by GABA in rat striatal slices. Brain Res. 1978; 139(1):115-30. DOI: 10.1016/0006-8993(78)90064-1. View

18.

Olpe H, Koella W, Wolf P, Haas H . The action of baclofen on neurons of the substantia nigra and of the ventral tegmental area. Brain Res. 1977; 134(3):577-80. DOI: 10.1016/0006-8993(77)90834-4. View

19.

Jones G, Neal M . Selective inhibition of neuronal GABA uptake by cis-1,3-aminocyclohexane carboxylic acid. Nature. 1976; 264(5583):281-4. DOI: 10.1038/264281a0. View

20.

Olsen R, Ban M, Miller T, Johnston G . Chemical instability of the GABA antagonist bicuculline under physiological conditions. Brain Res. 1975; 98(2):383-7. DOI: 10.1016/0006-8993(75)90019-0. View