Please use this identifier to cite or link to this item:
Effects of inactivation of the lateral habenula on place conditioning in rats
Conditioned place preference
GABA receptor agonist
|Issue Date: ||2018-07-20 18:04:58 (UTC+8)|
|Abstract: || 個體面對不同的外部刺激選擇合宜的行為反應，同時對環境的變化具備行為調整與學習之能力有助於生物體的存活。中腦邊緣多巴胺系統在上述行為中扮演重要的角色，其涉及個體的酬賞動機與聯結學習等認知行為。根據神經解剖學與行為神經科學的研究，外側韁核可以調控中腦邊緣多巴胺系統進而影響酬賞相關的動機行為；迄今絕大多數研究是使用操作式制約行為作業檢測外側韁核的神經活動與酬賞相關行為的關係，較少研究探討抑制外側韁核對於多巴胺相關之古典式制約行為的影響。因此本研究透過藥理抑制的方式，探討外側韁核的GABA受體對於場地制約行為的影響。實驗一的結果顯示GABAa受體致效劑muscimol注入外側韁核無法引發場地制約偏好(CPP)。實驗二的結果同時將muscimol及GABAb受體致效劑baclofen混合液(B/M)注入外側韁核無法形成CPP，惟有增加藥物制約配對箱的自發性活動量。實驗三進行周邊注射安非它命(d-AMP)0.5, 1, 2 mg/kg的劑量反應，發現其無法令受試習得CPP，但有增加藥物配對箱的行為活動量。實驗四進行B/M注入外側韁核結合腹腔注射d-AMP，其可有效地使受試習得CPP。綜合上述的實驗結果顯示，單獨以GABA類受體致效劑抑制外側韁核或以較低劑量的d-AMP周邊注射，皆無法讓個體形成顯著的CPP，而須在這兩項藥物處置同時進行方得顯著的CPP，這意含抑制外側韁核可以增強個體對於藥物酬賞相關的古典式制約學習行為。|
The ability of appropriate reaction to different kinds of external stimuli as well as behavioral flexibility in cases of response reinforcement contingencies being changed are essential for survival. Such behaviors involved in reward motivation and associative learning are known to be mediated by the mesolimbic dopamine (DA) systems. In terms of anatomy and behavioral neuroscience, the lateral habenula (LHb) has been suggested to modulate reward-related behaviors that are mediated by the mesolimbic DA systems. While there have been a number of studies using operant conditioning task to Investigate the role of the LHb in reward-related behavior, less work has attended on the role of the LHb in reward-related behavior as measured by the tasks based on classical conditioning theory. Therefore, in the present study, we investigated the effects of inactivation of the LHb by using GABA agonists on place conditioning task. The results of Experiment 1 show that intra-LHb infusion of muscimol, a GABAa agonist, did not produce any significant place conditioning. The results of Experiment 2 show that a mixture of the GABAb and GABAa agonists, baclofen and muscimol (B/M), infused into the LHb did not establish any significant place conditioning; even with the enhanced locomotor activity observed in drug-paired chamber during the conditioning sessions. In Experiment 3, we examined the dose effects of d-amphetamine (d-AMP; 0, 0.5, 1, or 2 mg/kg; IP) on place conditioning, and there was no drug-induced conditioned place preference (CPP). Locomotor activity was enhanced by d-AMP in drug-paired chamber during the conditioning session. The results of Experiment 4 show that intra-LHb infusion of B/M combined with IP injection of d-AMP significantly induced CPP. These data demonstrated that neither intra-LHb infusion of GABA agonists alone nor systemic injection of d-AMP alone produced significant place conditioning, but a CPP was developed by two aforementioned drug treatments administered in combination. Thus, the inactivation of the LHb is indicated to facilitate the individual in acquiring task involved classical conditioning of drug reward to contextual cue.
|Reference: ||Akirav I, Raizel H, Maroun M (2006) Enhancement of conditioned fear extinction by infusion of the GABA(A) agonist muscimol into the rat prefrontal cortex and amygdala. Eur J Neurosci 23:758-764.|
Baker PM, Jhou T, Li B, Matsumoto M, Mizumori SJY, Stephenson-Jones M, Vicentic A (2016) The lateral habenula circuitry: reward processing and cognitive control. J Neurosci 36:11482-11488.
Baker PM, Raynor SA, Francis NT, Mizumori SJY (2017) Lateral habenula integration of proactive and retroactive information mediates behavioral flexibility. Neuroscience 345:89-98.
Bardo MT, Valone JM, Bevins RA (1999) Locomotion and conditioned place preference produced by acute intravenous amphetamine: role of dopamine receptors and individual differences in amphetamine self-administration. Psychopharmacology 143:39-46.
Bressel PJRD, McNally GP (2014) The role of the lateral habenula in punishment. PLoS One 9:e111699.
Bromberg-Martin ES, Hikosaka O (2011) Lateral habenula neurons signal errors in the prediction of reward information. Nat Neurosci 14:1209-1216.
Bromberg-Martin ES, Matsumoto M, Hikosaka O (2010) Dopamine in motivational control: rewarding, aversive, and alerting. Neuron 68:815-834.
Budygin EA, Brodie MS, Sotnikova TD, Mateo Y, John CE, Cyr M, Gainetdinov RR, Jones SR (2004) Dissociation of rewarding and dopamine transporter-mediated properties of amphetamine. Proc Natl Acad Sci USA 101:7781-7786.
Cabib S, Puglisi-Allegra S, Genua C, Simon H, Le Moal M, Piazza PV (1996) Dose-dependent aversive and rewarding effects of amphetamine as revealed by a new place conditioning apparatus. Psychopharmacology 125:92-96.
Carr GD, Fibiger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. In: The neuropharmacological basis of reward (Liebman JM, Cooper SJ, eds), pp 264-319. New York: Oxford UP.
Christoph GR, Leonzio RJ, Wilcox KS (1986) Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat. J Neurosci 6:613-619.
Cunningham CL, Gremel CM, Groblewski PA (2006) Drug-induced conditioned place preference and aversion in mice. Nat Protoc 4:1662-1670.
Duchesne V, Boye SM (2013) Differential contribution of mesoaccumbens and mesohabenular dopamine to intracranial self-stimulation. Neuropharmacology 70:43-50.
Fakhoury M, Domínguez López S (2014) The Role of Habenula in Motivation and Reward. Adv in Neurosci 2014.
Friedman A, Lax E, Dikshtein Y, Abraham L, Flaumenhaft Y, Sudai E, Ben-Tzion M, Ami-Ad L, Yaka R, Yadid G (2010) Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior. Neuropharmacology 59:452-459.
Friedman A, Lax E, Dikshtein Y, Abraham L, Flaumenhaft Y, Sudai E, Ben-Tzion M, Yadid, G (2011) Electrical stimulation of the lateral habenula produces an inhibitory effect on sucrose self-administration. Neuropharmacology 60:381-387.
Gifuni AJ, Jozaghi S, Gauthier-Lamer AC, Boye SM (2012) Lesions of the lateral habenula dissociate the reward-enhancing and locomotor-stimulant effects of amphetamine. Neuropharmacology 63:945-957.
Gill MJ, Ghee SM, Harper SM, See RE (2013) Inactivation of the lateral habenula reduces anxiogenic behavior and cocaine seeking under conditions of heightened stress. Pharmacol Biochem Behav 111:24-29.
Golden SA, Heshmati M, Flanigan M, Christoffel DJ, Guise K, Pfau ML, Aleyasin H, Menard C, Zhang H, Hodes GE, Bregman D, Khibnik L, Tai J, Rebusi N, Krawitz B, Chaudhury D, Walsh JJ, Han MH, Shapiro ML, Russo SJ (2016) Basal forebrain projections to the lateral habenula modulate aggression reward. Nature 534:688-692.
Hasanein P, Mirazi N, Javanmardi K (2008) GABAA receptors in thecentral nucleus of amygdala (CeA) affect on pain modulation. Brain Res 1241:36-41.
Hikosaka O (2010) The habenula: from stress evasion to value-based decision-making. Nat Rev Neurosci 11:503-513.
Kuczenski R, Segal DS (1990) In vivo measures of monoamines during amphetamine-induced behaviors in rats. Prog Neuropsychopharmacol Biol Psychiatry 14:S37-S50.
Kuczenski R, Segal DS, Aizenstein ML (1991) Amphetamine, cocaine, and fencamfamine: relationship between locomotor and stereotypy response profiles and caudate and accumbens dopamine dynamics. J Neurosci 11:2703-2712.
Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM, Deisseroth K, Malenka RC (2012) Input-specific control of reward and aversion in the ventral tegmental area. Nature 491:212-217.
Laviola G, Dell’Omo G, Chiarotti G, Bignami G (1994) d-Amphetamine conditioned place preference in developing mice: relations with changes in activity and stereotypies. Behav Neurosci 108:514-524.
Lecca S, Meye FJ, Mameli M (2014) The lateral habenula in addiction and depression: an anatomical, synaptic and behavioral overview. Eur J Neurosci 39:1170-1178.
Lecourtier L, Defrancesco A, Moghaddam B (2008) Differential tonic influence of lateral habenula on prefrontal cortex and nucleus accumbens dopamine release. Eur J Neurosci 27:1755-1762.
Lecourtier L, Neijt HC, Kelly PH (2004) Habenula lesions cause impaired cognitive performance in rats: implications for schizophrenia. Eur J Neurosci 19:2551-2560.
Lee EH, Huang SL (1988) Role of lateral habenula in the regulation of exploratory behavior and its relationship to stress in rats. Behav Brain Res 30:265-271.
Lee YA, Goto Y (2011) Neurodevelopmental disruption of cortico-striatal function caused by degeneration of habenula neurons. PLoS One 6:e19450.
Lett BT (1988) Enhancement of conditioned preference for a place paired with amphetamine produced by blocking the association between place and amphetamine-induced sickness. Psychopharmacology 95:390-394.
Liao RM (2008) Development of conditioned place preference induced by intra-accumbens infusion of amphetamine is attenuated by co-infusion of dopamine D1 and D2 receptor antagonists. Pharmacol Biochem Behav 89:367-373.
Liao RM, Chang YH, Wang SH (1998) Inﬂuence of SCH23390 and Spiperone on the expression of conditioned place preference induced by d-amphetamine or cocaine. Chin J Physiol 41:85-92.
Liao RM, Chang YH, Wang SH, Lan CH (2000) Distinct accumbal subareas are involved in place conditioning of amphetamine and cocaine. Life Sci 67:2033-2043.
Li K, Zhou T, Liao L, Yang Z, Wong C, Henn F, Malinow R, Yates JR 3rd., Hu H (2013) βCaMKII in lateral habenula mediates core symptoms of depression. Science 341:1016-1020.
Mathis V, Barbelivien A, Majchrzak M, Mathis C, Cassel JC, Lecourtier L (2016) The Lateral Habenula as a Relay of Cortical Information to Process Working Memory. Cereb Cortex 13:1-11.
Mathis V, Cosquer B, Avallone M, Cassel JC, Lecourtier L (2015) Excitatory transmission to the lateral habenula is critical for encoding and retrieval of spatial memory. Neuropsychopharmacology 40:2843-2851.
Matsumoto M, Hikosaka O (2007) Lateral habenula as a source of negative reward signals in dopamine neurons. Nature 447:1111-1115.
Meye FJ, Lecca S, Valentinova K, Mameli M (2013) Synaptic and cellular profile of neurons in the lateral habenula. Front Hum Neurosci 7:860.
Meye FJ, Soiza-Reilly M, Smit T, Diana MA, Schwarz MK, Mameli M (2016) Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse. Nat Neurosci 19:1019-1024.
Money KM, Stanwood GD (2013) Developmental origins of brain disorders: roles for dopamine. Front Cell Neurosci 7:260.
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.
Omelchenko N, Bell R, Sesack SR (2009) Lateral habenula projections to dopamine GABA neurons in the rat ventral and tegmental area. Eur J Neurosci 30:1239-1250.
Pavlov IP (1927) Conditioned reflexes: An investigation of the physiological activity ofthe cerebral cortex. Trans and ed GV Anrep London: Oxford University Press.
Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. San Diego: Academic Press.
Proulx CD, Hikosaka O, Malinow R (2014) Reward processing by the lateral habenula in normal and depressive behaviors. Nat Neurosci 17:1146-1152.
Prus A, James JR, Rosecrans JA (2009) Conditioned Place Preference. Methods of Behavioral Analysis in Neuroscience. J Buccafusco Boca Raton (FL), CRC Press.
Rademacher DJ, Kovacs B, Shen F, Napier TC, Meredith GE (2006) The neural substrates of amphetamine conditioned place preference: implications for the formation of conditioned stimulus-reward associations. Eur J Neurosci 24:2089-2097.
Reicher MA, Holman EW (1977) Location preference and flavor aversion reinforced by amphetamine in rats. Animal Learning & Behavior 5:343-346.
Root DH, Mejias-Aponte CA, Zhang S, Wang HL, Hoffman AF, Lupica CR, Morales M (2014a) Single rodent mesohabenular axons release glutamate and GABA. Nat Neurosci 17:1543-1551.
Root DH, Mejias-Aponte CA, Qi J, Morales M (2014b) Role of glutamatergic projections from ventral tegmental area to lateral habenula in aversive conditioning. J Neurosci 34:13906-13910.
Rünkorg K, Värv S, Matsui T, Kõks S, Vasar E (2006) Differences in behavioural effects of amphetamine and dopamine-related gene expression in wild-type and homozygous CCK 2 receptor deficient mice. Neuroscience letters 406:17-22.
Salamone JD, Correa M (2012) The mysterious motivational functions of mesolimbic dopamine. Neuron 76:470-485.
Samson HH, Chappell A (2001) Muscimol injected into the medial prefrontal cortex of the rat alters ethanol self-administration. Physiol Behav 74:581-587.
Sanchis-Segura C, Spanagel R (2006) Behavioural assessment of drug reinforcement and addictive features in rodents: an overview. Addict Biol 11:2-38.
Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275:1593-1599.
Schultz W (2013) Updating dopamine reward signals. Curr Opin Neurobiol 23:229-238.
Shabel SJ, Proulx CD, Trias A, Murphy RT, Malinow R (2012) Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin. Neuron 74:475-481.
Shabel SJ, Proulx CD, Piriz J, Malinow R (2014) GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment. Science 345:1494-1498.
Shen YL, Chang TY, Chang YC, Tien HH, Yang FC, Wang PY,
Liao RM (2014) Elevated BDNF mRNA expression in the medial prefrontal cortex after d-amphetamine reinstated conditioned place preference in rats. Neuroscience 263:88-95.
Sitte HH, Freissmuth M (2015) Amphetamines, new psychoactive drugs and the monoamine transporter cycle. Trends Pharmacol Sci 36:41-50.
Smith Y, Séguéla P, Parent A (1987) Distribution of GABA-immunoreactive neurons in the thalamus of the squirrel monkey (Saimiri sciureus). Neuroscience 22:579-591.
Song M, Jo YS, Lee YK, Cho JS (2017) Lesions of the lateral habenula facilitate active avoidance learning and threat extinction. Behav Brain Res 318:12-17.
Sun JY, Yang JY, Wang F, Hou Y, Dong YX, Wu CF (2011) GABAA receptors in VTA mediate the morphine-induced release of ascorbic acid in rat nucleus accumbens. Brain Res 1368:52-58.
Spyraki C, Fibiger HC, Phillips AG (1982) Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res 253:185-193.
Stamatakis AM, Stuber GD (2012) Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance. Nat Neurosci 15:1105-1107.
Stamatakis AM, Jennings JH, Ung RL, Blair GA, Weinberg RJ, Neve RL, Boyce F, Mattis J, Ramakrishnan C, Deisseroth K, Stuber GD (2013) A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward. Neuron 80:1039-1053.
Stamatakis AM, Van Swieten M, Basiri ML, Blair GA, Kantak P, Stuber GD (2016) Lateral hypothalamic area glutamatergic neurons and their projections to the lateral habenula regulate feeding and reward. J Neurosci 36:302-311.
Stopper CM, Floresco SB (2014) What’s better for me? Fundamental role for lateral habenula in promoting subjective decision biases. Nat Neurosci 17:33-35.
Stopper CM, Maric TL, Montes DR, Wiedman CR, Floresco SB (2014) Overriding phasic dopamine signals redirects action selection during risk/reward decision making. Neuron 84:177-189.
Thornton EW, Bradbury GE, Davies C (1990) Increased immobility in an automated forced swimming test following lesion of the habenula in rats: Absence of evidence for a contribution from motor impairment. Behav Neurosci 104:37-43.
Tian J, Uchida N (2015) Habenula lesions reveal that multiple mechanisms underlie dopamine prediction errors. Neuron 87:1304-1316.
Tomaiuolo M, Gonzalez C, Medina JH, Piriz J (2014) Lateral Habenula determines long-term storage of aversive memories. Front Behav Neurosci 8:170.
van Kerkhof LWM, Damsteegt R, Trezza V, Voorn P, Vanderschuren LJMJ (2013b) Functional integrity of the habenula is necessary for social play behavior in adolescent rats. Eur J Neurosci 38:3465-3475.
Velasquez M, Molfese DL, Salas R (2014) The role of the habenula in drug addiction. Front Hum Neurosci 8:174.
Wang D, Li Y, Feng Q, Guo Q, Zhou J, Luo M (2017) Learning shapes the aversion and reward responses of lateral habenula neurons. eLife 6:e23045.
Wang T, Zhang L, Zhang QJ, Wang Y, Du CX, Sun YN, Zhang J, Lv SX, Chen L, Liu J (2017) Involvement of lateral habenula α1 subunit-containing GABAA receptor-mediated inhibitory transmission in the regulation of depression-related behaviors in experimental Parkinson's disease. Neuropharmacology 116:399-411.
Wang Z, Wang L, Yamamoto R, Sugai T, Kato N (2013) Role of the lateral habenula in shaping context-dependent locomotor activity during cognitive tasks. Neuroreport 24:276-280.
Weiss T, Veh RW (2011) Morphological and electrophysiological characteristics of neurons within identified subnuclei of the lateral habenula in rat brain slices. Neuroscience 172:74-93.
Winter C, Vollmayr B, Djodari-Irani A, Klein J, Sartorius A (2011) Pharmacological inhibition of the lateral habenula improves depressive-like behavior in an animal model of treatment resistant depression. Behav Brain Res 216:463-465.
Wise RA (1982) Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 5:39.
Zapata A, Hwang EK, Lupica CR (2017) Lateral Habenula Involvement in Impulsive Cocaine Seeking. Neuropsychopharmacology 42:1103-1112.
|Source URI: ||http://thesis.lib.nccu.edu.tw/record/#G1037540101|
|Data Type: ||thesis|
|Appears in Collections:||[神經科學研究所 ] 學位論文|
Files in This Item:
All items in 政大典藏 are protected by copyright, with all rights reserved.