Abstract
In a previous study, systemic administration of the GABAB receptor agonist, R-(+)-baclofen (2.5 mg/kg, i.p.) blocked acute amphetamine (2.5 mg/kg, i.p.)-induced rearing and neuropeptide (preprodynorphin (PPD), preprotachykinin (PPT), preproenkephalin (PPE), and secretogranin II (SGII)) mRNA expression in the striatum (Zhou et al, 2004). The purpose of the present study was to investigate the site(s) of action of these baclofen effects in the dorsal and ventral striatal circuitries. Infusion of baclofen (75 ng/side) into the ventral tegmental area (VTA), substantia nigra (SN), nucleus accumbens (NA), caudate-putamen (Cpu), or medial prefrontal cortex (mPFC) had no effect on behavioral activity in saline-treated rats habituated to a photocell apparatus. However, intra-VTA infusion of baclofen (75 ng/side) completely blocked, whereas intra-NA and intra-SN infusion of baclofen attenuated, amphetamine-induced vertical activity without affecting amphetamine-induced total distance traveled. In contrast, intramedial PFC and intra-CPu infusion of baclofen had no effect on behavioral activity in amphetamine-treated rats. Infusion of baclofen into the VTA, NA, or SN decreased amphetamine-induced neuropeptide gene expression in the striatum. These results indicate that GABAB receptor stimulation within the ventral striatal circuitry is involved in mediating acute amphetamine-induced behaviors and neuropeptide gene expression in the dorsal and ventral striatum. The present study provides information on the potential targets in the brain for baclofen in the initial behavioral and genomic response to amphetamine.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Anderson JJ, Kuo S, Chase TN, Engber TM (1994). Dopamine D1 receptor-stimulated release of acetylcholine in rat striatum is mediated indirectly by activation of striatal neurokinin1 receptors. J Pharmacol Exp Ther 269: 1144–1151.
Balon N, Kriem B, Weiss M, Rostain JC (2002). GABAA receptors in the pars compacta and GABAB receptors in the pars reticulata of rat substantia nigra modulate striatal dopamine release. Neurochem Res 27: 373–379.
Bowery NG (1993). GABAB receptor pharmacology. Annu Rev Pharmacol Toxicol 33: 109–147.
Boyes J, Bolam JP (2003). The subcellular localization of GABA(B) receptor subunits in the rat substantia nigra. Eur J Neurosci 18: 3279–3293.
Brebner K, Childress AR, Roberts DC (2002). A potential role for GABA(B) agonists in the treatment of psychostimulant addiction. Alcohol Alcohol 37: 478–484.
Brebner K, Phelan R, Roberts DC (2000). Effect of baclofen on cocaine self-administration in rats reinforced under fixed-ratio 1 and progressive-ratio schedules. Psychopharmacology (Berlin) 148: 314–321.
Campbell UC, Lac ST, Carroll ME (1999). Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats. Psychopharmacology (Berlin) 143: 209–214.
Charara A, Heilman C, Levey AI, Smith Y (2000). Pre- and postsynaptic localization of GABAB receptors in the basal ganglia of monkeys. Neuroscience 95: 127–140.
Chu DC, Albin RL, Young AB, Penney JB (1990). Distribution and kinetics of GABAB binding sites in rat central nervous system: a quantitative autoradiographic study. Neuroscience 34: 341–357.
Clarke PB, Jakubovic A, Fibiger HC (1988). Anatomical analysis of the involvement of mesolimbocortical dopamine in the locomotor stimulant actions of d-amphetamine and apomorphine. Psychopharmacology (Berlin) 96: 511–520.
Creese I, Iversen SD (1972). Amphetamine response in rat after dopamine neurone destruction. Nat New Biol 238: 247–248.
Darracq L, Blanc G, Glowinski J, Tassin JP (1998). Importance of the noradrenaline-dopamine coupling in the locomotor activating effects of D-amphetamine. J Neurosci 18: 2729–2739.
Dickson PR, Lang CG, Hinton SC, Kelley AE (1994). Oral stereotypy induced by amphetamine microinjection into striatum: an anatomical mapping study. Neuroscience 61: 81–91.
Engberg G, Kling-Petersen T, Nissbrandt H (1993). GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra. Synapse 15: 229–238.
Erhardt S, Mathe JM, Chergui K, Engberg G, Svenson TH (2002). GABAB receptor-mediated modulation of the firing pattern of ventral tegmental area dopamine neurons in vivo. NS Arch Pharmacol 365: 173–180.
Fadda P, Scherma M, Fresu A, Collu M, Fratta W (2003). Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of the rat. Synapse 50: 1–6.
Fink JS, Smith GP (1980). Mesolimbic and mesocortical dopaminergic neurons are necessary for normal exploratory behavior in rats. Neurosci Lett 17: 61–65.
Gerfen CR, Herkenham M, Thibault T (1987). The neostriatal mosaic II: patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. J Neurosci 7: 3915–3934.
Gonzalez-Nicolini V, McGinty JF (2002). Gene expression profile from the striatum of amphetamine-treated rats: a cDNA array and in situ hybridization histochemical study. Brain Res Gene Expression Patterns 1: 193–198.
Gray AM, Rawls SM, Shippenberg TS, McGinty JF (1999). The kappa-opioid agonist, U-69593, decreases acute amphetamine-evoked behaviors and calcium-dependent dialysate levels of dopamine and glutamate in the ventral striatum. J Neurochem 73: 1066–1074.
Guzman RG, Kendrick KM, Emson PC (1993). Effect of substance P on acetylcholine and dopamine release in the rat striatum: a microdialysis study. Brain Res 622: 147–154.
Haber SN, Fudge JL, McFarland NR (2000). Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci 20: 2369–2382.
Hanson GR, Bush L, Keefe KA, Alburges ME (2002). Distinct responses of basal ganglia substance P systems to low and high doses of methamphetamine. J Neurochem 82: 1171–1178.
Heijna MH, Padt M, Hogenboom F, Portoghese PS, Mulder AH, Schoffelmeer AN (1990). Opioid receptor-mediated inhibition of dopamine and acetylcholine release from slices of rat nucleus accumbens, olfactory tubercle and frontal cortex. Eur J Pharmacol 181: 267–278.
Heimer L, Zahm DS, Churchill L, Kalivas PW, Wohltmann C (1991). Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41: 89–125.
Huttner WB, Gerdes HH, Rosa P (1991). The granin (chromogranin/secretogranin) family. Trends Biochem Sci 16: 27–30.
Kalivas PW, Duffy P, Eberhardt H (1990). Modulation of A10 dopamine neurons by gamma-aminobutyric acid agonists. J Pharmacol Exp Ther 253: 858–866.
Kalivas PW, Stewart J (1991). Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Rev 16: 223–244.
Karler R, Chaudhry IA, Calder LD, Turkanis SA (1990). Amphetamine behavioral sensitization and the excitatory amino acids. Brain Res 537: 76–82.
Kelly PH, Seviour PW, Iversen SD (1975). Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94: 507–522.
Koob GF, Stinus L, Le Moal M (1981). Hyperactivity and hypoactivity produced by lesions to the mesolimbic dopamine system. Behav Brain Res 3: 341–359.
Lopez-Bendito G, Shigemoto R, Kulik A, Paulsen O, Fairen A, Lujan R (2002). Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development. Eur J Neurosci 15: 1766–1778.
Loughlin SE, Fallon JH (1982). Mesostriatal projections from ventral tegmentum and dorsal raphe: cells project ipsilaterally or contralaterally but not bilaterally. Neurosci Lett 32: 11–16.
Misgeld U, Bijak M, Jarolimek W (1995). A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog Neurobiol 46: 423–462.
Nauta WHJ, Smith GP, Faull RLM, Domesick VB (1978). Efferent connections and nigral afferents of the nucleus accumbens septi in the rat. Neuroscience 3: 385–401.
Nisenbaum ES, Berger TW, Grace AA (1993). Depression of glutamatergic and GABAergic synaptic responses in striatal spiny neurons by stimulation of presynaptic GABAB receptors. Synapse 14: 221–242.
Paredes D, Catlow B, McGinty JF (2001). Amphetamine-induced increase in dopamine levels in dorsal striatum in vivo is partially sodium-dependent. Soc Neurosci Abstr 744: 11.
Paxinos G, Watson C (1986). The Rat Brain in Stereotaxic Coordinates. Academic Press: San Diego.
Rawls SM, McGinty JF (2000). Delta opioid receptors regulate calcium-dependent, amphetamine-evoked glutamate levels in the rat striatum: an in vivo microdialysis study. Brain Res 861: 296–304.
Roberts DC, Andrews MM (1997). Baclofen suppression of cocaine self-administration: demonstration using a discrete trials procedure. Psychopharmacology (Berlin) 131: 271–277.
Roberts DC, Andrews MM, Vickers GJ (1996). Baclofen attenuates the reinforcing effects of cocaine in rats. Neuropsychopharmacology 15: 417–423.
Robinson TE, Becker JB (1986). Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 396: 157–198.
Santiago M, Machado A, Cano J (1993). In vivo release of dopamine from rat striatum, substantia nigra and prefrontal cortex: differential modulation by baclofen. Br J Pharmacol 109: 814–818.
Schneider LH, Alpert JE, Iversen SD (1983). CCK-8 modulation of mesolimbic dopamine: antagonism of amphetamine-stimulated behaviors. Peptides 4: 749–753.
Sharp T, Zetterstrom T, Ljungberg T, Ungerstedt U (1987). A direct comparison of amphetamine-induced behaviours and regional brain dopamine release in the rat using intracerebral dialysis. Brain Res 401: 322–330.
Shoaib M, Swanner LS, Beyer CE, Goldberg SR, Schindler CW (1998). The GABAB agonist baclofen modifies cocaine self-administration in rats. Behav Pharmacol 9: 195–206.
Shoptaw S, Yang X, Rotheram-Fuller EJ, Hsieh YC, Kintaudi PC, Charuvastra VC et al (2003). Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use. J Clin Psychiatry 64: 1440–1448.
Sugita S, Johnson SW, North RA (1992). Synaptic inputs to GABAA and GABAB receptors originate from discrete afferent neurons. Neurosci Lett 134: 207–211.
Tzschentke TM, Schmidt WJ (1998). Discrete quinolinic acid lesions of the rat prelimbic medial prefrontal cortex affect cocaine- and MK-801-, but not morphine- and amphetamine-induced reward and psychomotor activation as measured with the place preference conditioning paradigm. Behav Brain Res 97: 115–127.
Vanderschuren LJ, Kalivas PW (2000). Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology (Berlin) 151: 99–120.
Ventura R, Cabib S, Alcaro A, Orsini C, Puglisi-Allegra S (2003). Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release. J Neurosci 23: 1879–1885.
Wang JQ, Daunais JB, McGinty JF (1994a). Role of kainate/AMPA receptors in induction of striatal transcription factor and preprodynorphin mRNA by a single injection of amphetamine. Mol Brain Res 27: 118–126.
Wang JQ, Daunais JB, McGinty JF (1994b). NMDA receptors mediate amphetamine-induced upregulation of zif/268 and preprodynorphin mRNA expression in rat striatum. Synapse 18: 43–353.
Wang JQ, McGinty JF (1995a). Alterations in striatal zif/268, preprodynorphin and preproenkephalin mRNA expression induced by repeated amphetamine administration in rats. Brain Res 673: 262–274.
Wang JQ, McGinty JF (1995b). Dose-dependent alteration in zif/268 and preprodynorphin mRNA expression induced by amphetamine or methamphetamine in rat forebrain. J Pharmacol Exp Ther 273: 909–917.
Wang JQ, McGinty JF (1996). Intrastriatal injection of the metabotropic glutamate receptor antagonist MCPG attenuates acute amphetamine-stimulated neuropeptide mRNA expression in rat striatum. Neurosci Lett 218: 13–16.
Wang JQ, McGinty JF (1997). Intrastriatal injection of a muscarinic receptor agonist and antagonist regulates striatal neuropeptide mRNA expression in normal and amphetamine-treated rats. Brain Res 748: 62–70.
Westerink BHC, Santiago M, de Vries JB (1992). In vivo evidence for a concordant response of terminal and dendritic dopamine relase during intranigral infusion of drugs. NS Arch Pharmacol 346: 637–643.
White FJ, Wolf ME (1991). Psychomotor stimulants. In: Pratt JA (ed). The Biological Basis of Drug Tolerance and Dependence. Academic Press: London, pp 153–197.
Zahm DS, Heimer L (1993). Specificity in the efferent projections of the nucleus accumbens in the rat: comparison of the rostral pole projection patterns with those of the core and shell. J Comp Neurol 327: 220–232.
Zetterstrom T, Sharp T, Marsden CA, Ungerstedt U (1983). In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine. J Neurochem 41: 1769–1773.
Zhou W, Mailloux AW, Jung BJ, Edmunds Jr HS, McGinty JF (2004). GABA(B) receptor stimulation decreases amphetamine-induced behavior and neuropeptide gene expression in the striatum. Brain Res 1004: 18–28.
Acknowledgements
We thank Ms Lan Jin for her technical assistance. This work was supported by DA03982.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhou, W., Mailloux, A. & McGinty, J. Intracerebral Baclofen Administration Decreases Amphetamine-Induced Behavior and Neuropeptide Gene Expression in the Striatum. Neuropsychopharmacol 30, 880–890 (2005). https://doi.org/10.1038/sj.npp.1300635
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.npp.1300635
Keywords
This article is cited by
-
GABAB receptor cell-surface export is controlled by an endoplasmic reticulum gatekeeper
Molecular Psychiatry (2016)
