Abstract
Rationale
Reinforcement in the medial septal division (MSDB) might involve local GABAergic mechanisms.
Objectives
We used intracranial self-administration to determine whether the GABAA agonist muscimol or antagonist bicuculline might have rewarding effects when infused into the MSDB. We assessed the anatomical specificity of muscimol intra-MSDB self-administration by injecting this molecule into the nucleus accumbens (NAc). Finally, we evaluated the involvement of dopaminergic mechanisms in muscimol self-administration.
Materials and methods
BALB/c mice were implanted with a guide cannula targeting the MSDB or the NAc. They were trained to discriminate between the two arms of a Y-maze, one arm being reinforced by muscimol or bicuculline injections. Another group of MSDB implanted mice was pre-treated intraperitoneally before muscimol self-administration with a D1 (SCH23390) or D2/D3 (sulpiride) receptor antagonist or vehicle. A last group of MSDB mice received additional bilateral guide cannulae targeting the ventral tegmental area (VTA) or a more dorsal region to assess the effects of intra-VTA injection of SCH23390 on intra-MSDB muscimol self-administration.
Results
Mice self-administered intra-MSDB muscimol (0.6, 1.2, or 12 ng/50 nl), but not bicuculline (1.5 or 3 ng/50 nl). Systemic pre-treatment with SCH23390 (25 μg/kg) or sulpiride (50 mg/kg) or bilateral injection of SCH23390 (0.25 μg/0.1 μl) into the VTA prevented acquisition of intra-MSDB muscimol self-administration.
Conclusion
The activation of GABAA receptors in the MSDB supports self-administration, and dopamine release from the VTA may be involved in the acquisition of this behaviour. The MSDB could represent a common brain substrate for the rewarding properties of drugs facilitating GABAA tone.
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References
Allen CN, Crawford IL (1984) GABAergic agents in the medial septal nucleus affect hippocampal theta rhythm and acetylcholine utilization. Brain Res 322:261–267
Berridge KC, Robinson TE (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev 28:309–369
Borhegyi Z, Freund TF (1998) Dual projection from the medial septum to the supramammillary nucleus in the rat. Brain Res Bull 46:453–459
Bozart MA (1983) Opiate reward mechanism mapped by intracranial self-administration. In: Smith JE (ed) Neurbiology of reward processes, L.J.D. Amsterdam, Elsevier, pp 331–359
Cardinal RN, Parkinson JA, Hall J, Everitt BJ (2002) Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev 26:321–352
Cazala P, Galey D, Durkin T (1988) Electrical self-stimulation in the medial and lateral septum as compared to the lateral hypothalamus: differential intervention of reward and learning processes? Physiol Behav 44:53–59
Cazala P, Norena A, Le Merrer J, Galey D (1998) Differential involvement of the lateral and medial divisions of the septal area on spatial learning processes as revealed by intracranial self-administration of morphine in mice. Behav Brain Res 97:179–188
Chang Q, Savage LM, Gold PE (2006) Microdialysis measures of functional increases in ACh release in the hippocampus with and without inclusion of acetylcholinesterase inhibitors in the perfusate. J Neurochem 97:697–706
Colom LV, Castaneda MT, Reyna T, Hernandez S, Garrido-Sanabria E (2005) Characterization of medial septal glutamatergic neurons and their projection to the hippocampus. Synapse 58:151–164
David V, Durkin TP, Cazala P (1997) Self-administration of the GABAA antagonist bicuculline into the ventral tegmental area in mice: dependence on D2 dopaminergic mechanisms. Psychopharmacology (Berl) 130:85–90
Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114
Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489
Floresco SB, Todd CL, Grace AA (2001) Glutamatergic afferents from the hippocampus to the nucleus accumbens regulate activity of ventral tegmental area dopamine neurons. J Neurosci 21:4915–4922
Gao B, Hornung JP, Fritschy JM (1995) Identification of distinct GABAA-receptor subtypes in cholinergic and parvalbumin-positive neurons of the rat and marmoset medial septum-diagonal band complex. Neuroscience 65:101–117
Geisler S, Zahm DS (2005) Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions. J Comp Neurol 490:270–294
Geisler S, Derst C, Veh RW, Zahm DS (2007) Glutamatergic afferents of the ventral tegmental area in the rat. J Neurosci 27:5730–5743
Grace AA, Floresco SB, Goto Y, Lodge DJ (2007) Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci 30:220–227 Epub 2007 Apr 2
Heidbreder CA, Groenewegen HJ (2003) The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics. Neurosci Biobehav Rev 27:555–579
Henderson Z (1995) Expression of GABAA receptor subunit messenger RNA in non-cholinergic neurons of the rat basal forebrain. Neuroscience 65:1077–1086
Ikemoto S (2005) The supramammillary nucleus mediates primary reinforcement via GABA(A) receptors. Neuropsychopharmacology 30:1088–1095
Ikemoto S, Panksepp J (1994) The relationship between self-stimulation and sniffing in rats: does a common brain system mediate these behaviors? Behav Brain Res 61:143–162
Ikemoto S, Murphy JM, McBride WJ (1997) Self-infusion of GABA(A) antagonists directly into the ventral tegmental area and adjacent regions. Behav Neurosci 111:369–380
Jakab RL, Leranth C (1995) Septum. In: Paxinos G (ed) The rat nervous system. vol. 20. New York, Academic, pp 405–442
Jinno S, Kosaka T (2002) Immunocytochemical characterization of hippocamposeptal projecting GABAergic nonprincipal neurons in the mouse brain: a retrograde labeling study. Brain Res 945:219–231
Klemm WR (2004) Habenular and interpeduncularis nuclei: shared components in multiple-function networks. Med Sci Monit 10:RA261–73 Epub 2004 Oct 26
Kobayashi Y, Okada K (2007) Reward prediction error computation in the pedunculopontine tegmental nucleus neurons. Ann N Y Acad Sci 1104:310–323 Epub 2007 Mar 7
Le Merrer J, Gavello-Baudy S, Galey D, Cazala P (2007) Morphine self-administration into the lateral septum depends on dopaminergic mechanisms: evidence from pharmacology and Fos neuroimaging. Behav Brain Res 180:203–217 Epub 2007 Mar 16
Lisman JE, Grace AA (2005) The hippocampal-VTA loop: controlling the entry of information into long-term memory. Neuron 46:703–713
Liu ZH, Ikemoto S (2007) The midbrain raphe nuclei mediate primary reinforcement via GABA(A) receptors. Eur J Neurosci 25:735–743
Manseau F, Danik M, Williams S (2005) A functional glutamatergic neurone network in the medial septum and diagonal band area. J Physiol 566:865–884
Moor E, DeBoer P, Westerink BH (1998a) GABA receptors and benzodiazepine binding sites modulate hippocampal acetylcholine release in vivo. Eur J Pharmacol 359:119–126
Moor E, Schirm E, Jacso J, Westerink BH (1998b) Involvement of medial septal glutamate and GABAA receptors in behaviour-induced acetylcholine release in the hippocampus: a dual probe microdialysis study. Brain Res 789:1–8
Oades RD, Halliday GM (1987) Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res 434:117–165
Olds J, Milner P (1954) Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiol Psychol 47:419–427
Osborne PG (1994) A GABAergic mechanism in the medial septum influences cortical arousal and locomotor activity but not a previously learned spatial discrimination task. Neurosci Lett. 173:63–66
Pan WX, McNaughton N (2004) The supramammillary area: its organization, functions and relationship to the hippocampus. Prog Neurobiol 74:127–166
Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates. San Diego, Academic
Ranaldi R, Wise RA (2001) Blockade of D1 dopamine receptors in the ventral tegmental area decreases cocaine reward: possible role for dendritically released dopamine. J Neurosci 21:5841–5846
Redgrave P, Gurney K (2006) The short-latency dopamine signal: a role in discovering novel actions? Nat Rev Neurosci 7:967–975
Reynolds SM, Berridge KC (2002) Positive and negative motivation in nucleus accumbens shell: bivalent rostrocaudal gradients for GABA-elicited eating, taste “liking”/“disliking” reactions, place preference/avoidance, and fear. J Neurosci 22:7308–7320
Risold PY, Swanson LW (1996) Structural evidence for functional domains in the rat hippocampus. Science 272:1484–1486
Risold PY, Swanson LW (1997) Chemoarchitecture of the rat lateral septal nucleus. Brain Res Brain Res Rev 24:91–113
Salamone JD, Correa M (2002) Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137:3–25
Schultz W (2002) Getting formal with dopamine and reward. Neuron 36:241–263
Schwerdtfeger WK, Buhl E (1986) Various types of non-pyramidal hippocampal neurons project to the septum and contralateral hippocampus. Brain Res 386:146–154
Sharf R, Lee DY, Ranaldi R (2005) Microinjections of SCH 23390 in the ventral tegmental area reduce operant responding under a progressive ratio schedule of food reinforcement in rats. Brain Res 1033:179–185
Sheehan TP, Chambers RA, Russell DS (2004) Regulation of affect by the lateral septum: implications for neuropsychiatry. Brain Res Brain Res Rev 46:71–117
Stein EA, Olds J (1977) Direct intracerebral self-administration of opiates in the rat. Soc Neurosci Abstr 3:302
Stein EA, Zerneskie J (1979) Is reward behavior mediated by an endogenous opiate system? Soc Neurosci Abstr 5:573
Swanson LW, Cowan WM (1979) The connections of the septal region in the rat. J Comp Neurol. 186:621–655
Vertes RP (2004) Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51:32–58
Vinogradova OS, Kitchigina VF, Kudina TA, Zenchenko KI (1999) Spontaneous activity and sensory responses of hippocampal neurons during persistent theta-rhythm evoked by median raphe nucleus blockade in rabbit. Neuroscience 94:745–753
Wise RA (2004) Dopamine, learning and motivation. Nat Rev Neurosci 5:483–494
Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492
Wise RA, Hoffman DC (1992) Localization of drug reward mechanisms by intracranial injections. Synapse 10:247–263
Wise RA, Spindler J, deWit H, Gerberg GJ (1978) Neuroleptic-induced “anhedonia” in rats: pimozide blocks reward quality of food. Science 201:262–264
Xi ZX, Stein EA (2002) GABAergic mechanisms of opiate reinforcement. Alcohol Alcohol 37:485–494
Acknowledgements
We thank Drs A. Pradhan, D. Massotte and T.P. Durkin for their helpful comments on a previous draft of this manuscript.
Conflict of interest
The authors declare that, except for income received from our primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.
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This investigation was supported by grants from the CNRS (UMR 5228).
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Gavello-Baudy, S., Le Merrer, J., Decorte, L. et al. Self-administration of the GABAA agonist muscimol into the medial septum: dependence on dopaminergic mechanisms. Psychopharmacology 201, 219–228 (2008). https://doi.org/10.1007/s00213-008-1263-z
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DOI: https://doi.org/10.1007/s00213-008-1263-z