Role of the mesoamygdaloid dopamine projection in emotional learning
Abstract
Rationale
Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier ‘emotional’ learning.
Objectives
A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed.
Methods
Experiment 1a presented a light paired (CS+ group) or unpaired (CS− group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 µl/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b).
Results
For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing.
Conclusions
Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent.
Keywords
Amygdala Dopamine Learning and memory Emotion Associative learning Behaviour Classical conditioning Consolidation RetrogradeNotes
Acknowledgements
This work was supported by Project Grants from the Medical Research Council and Wellcome Trust.
References
- Asan E (1998) The catecholaminergic innervation of the rat amygdala. Adv Anat Embryol Cell Biol 142:1–118PubMedGoogle Scholar
- Bardo MT, Bowling SL, Pierce RC (1990) Changes in locomotion and dopamine neurotransmission following amphetamine, haloperidol, and exposure to novel environmental stimuli. Psychopharmacology Berl 101:338–343PubMedCrossRefGoogle Scholar
- Blundell P, Hall G, Killcross S (2001) Lesions of the basolateral amygdala disrupt selective aspects of reinforcer representation in rats. J Neurosci 21:9018–9026PubMedGoogle Scholar
- Blundell P, Hall G, Killcross S (2003) Preserved sensitivity to outcome value after lesions of the basolateral amygdala. J Neurosci 23:7702–7709PubMedGoogle Scholar
- Burke KA, Franz TM, Miller DN, Schoenbaum G (2007) Conditioned reinforcement can be mediated by either outcome-specific or general affective representations. Front Integr Neurosci 1:2PubMedCrossRefGoogle Scholar
- Colwill RM, Motzkin DK (1994) Encoding of the unconditioned stimulus in Pavlovian conditioning. Anim Learn Behav 22:384–394Google Scholar
- Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489PubMedCrossRefGoogle Scholar
- Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW (1999) Associative processes in addiction and reward. The role of amygdala-ventral striatal subsystems. Ann N Y Acad Sci 877:412–438PubMedCrossRefGoogle Scholar
- Fleshler M, Hoffman HS (1962) A progression for generating variable-interval schedules. J Exp Anal Behav 5:529–530PubMedCrossRefGoogle Scholar
- Freedman LJ, Cassell MD (1994) Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat. Brain Res 633:243–252PubMedCrossRefGoogle Scholar
- Grace AA, Rosenkranz JA (2002) Regulation of conditioned responses of basolateral amygdala neurons. Physiol Behav 77:489–493PubMedCrossRefGoogle Scholar
- Greba Q, Gifkins A, Kokkinidis L (2001) Inhibition of amygdaloid dopamine D2 receptors impairs emotional learning measured with fear-potentiated startle. Brain Res 899:218–226PubMedCrossRefGoogle Scholar
- Harmer CJ, Phillips GD (1999) Enhanced dopamine efflux in the amygdala by a predictive, but not a non-predictive, stimulus: facilitation by prior repeated d-amphetamine. Neuroscience 90:119–130PubMedCrossRefGoogle Scholar
- Harmer CJ, Hitchcott PK, Morutto SL, Phillips GD (1997) Repeated d-amphetamine enhances stimulated mesoamygdaloid dopamine transmission. Psychopharmacology 132:247–254PubMedCrossRefGoogle Scholar
- Hinrichs JV, Ghoneim MM, Mewaldt SP (1984) Diazepam and memory: retrograde facilitation produced by interference reduction. Psychopharmacology 84:158–162PubMedCrossRefGoogle Scholar
- Hitchcott PK, Phillips GD (1998a) Double dissociation of the behavioural effects of R(+) 7-OH-DPAT infusions in the central and basolateral amygdala nuclei upon Pavlovian and instrumental conditioned appetitive behaviours. Psychopharmacology (Berl) 140:458–469CrossRefGoogle Scholar
- Hitchcott PK, Phillips GD (1998b) Effects of intra amygdala R(+) 7-OH-DPAT on intraaccumbens d-amphetamine-associated learning - I. Pavlovian conditioning. Psychopharmacology 140:300–309PubMedCrossRefGoogle Scholar
- Hitchcott PK, Phillips GD (1998c) Effects of intra-amygdala R(+) 7-OH-DPAT on intra-accumbens d-amphetamine-associated learning - II. Instrumental conditioning. Psychopharmacology 140:310–318PubMedCrossRefGoogle Scholar
- Hitchcott PK, Bonardi CM, Phillips GD (1997a) Enhanced stimulus-reward learning by intra-amygdala administration of a D3 dopamine receptor agonist. Psychopharmacology (Berl) 133:240–248CrossRefGoogle Scholar
- Hitchcott PK, Harmer CJ, Phillips GD (1997b) Enhanced acquisition of discriminative approach following intra-amygdala d-amphetamine. Psychopharmacology 132:237–246PubMedCrossRefGoogle Scholar
- Holland P (1998) Amount of training affects associatively-activated event representation. Neuropharmacology 37:461–469PubMedCrossRefGoogle Scholar
- Jones SR, Garris PA, Kilts CD, Wightman RM (1995) Comparison of dopamine uptake in the basolateral amygdaloid nucleus, caudate-putamen, and nucleus-accumbens of the rat. J Neurochem 64:2581–2589PubMedCrossRefGoogle Scholar
- Konorski J (1967) Integrative activity of the brain. University of Chicago Press, University of Chicago PressGoogle Scholar
- Lang PJ, Davis M (2006) Emotion, motivation, and the brain: reflex foundations in animal and human research. Prog Brain Res 156:3–29PubMedCrossRefGoogle Scholar
- Lennartz RC, Weinberger NM (1992) Analysis of response systems in Pavlovian conditioning reveals rapidly versus slowly acquired conditioned responses: support for two factors, implications for behavior and neurobiology. Psychobiology 20:93–119Google Scholar
- McDannald M, Kerfoot E, Gallagher M, Holland PC (2004) Amygdala central nucleus function is necessary for learning but not expression of conditioned visual orienting. Eur J NeuroSci 20:240–248PubMedCrossRefGoogle Scholar
- McGaugh JL (2000) Memory-a century of consolidation. Science 287:248–251PubMedCrossRefGoogle Scholar
- Mintz M, Wang-Ninio Y (2001) Two-stage theory of conditioning: involvement of the cerebellum and the amygdala. Brain Res 897:150–156PubMedCrossRefGoogle Scholar
- Mogenson GJ, Jones DL, Yim CY (1980) From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 14:69–97PubMedCrossRefGoogle Scholar
- Mueller CW, Lisman SA, Spear NE (1983) Alcohol enhancement of human memory: tests of consolidation and interference hypotheses. Psychopharmacology 80:226–230PubMedCrossRefGoogle Scholar
- Müller GE, Pilzecker A (1900) Experimentalle Beiträge zur Lehre vom Gedächtniss. Zeitschrift Fur Psychologie 1:1–288Google Scholar
- Murray AM, Ryoo HL, Gurevich E, Joyce JN (1994) Localization of dopamine D-3 receptors to mesolimbic and D-2 receptors to mesostriatal regions of human forebrain. Proc Natl Acad Sci USA 91:11271–11275PubMedCrossRefGoogle Scholar
- Ostlund SB, Winterbauer NE, Balleine B (2009) Theory of reward systems. In: Byrne JH (ed) Concise learning and memory. Academic, Amsterdam, pp 483–502Google Scholar
- Parker ES, Birnbaum IM, Weingartner H, Hartley JT, Stillman RC, Wyatt RJ (1980) Retrograde enhancement of human memory with alcohol. Psychopharmacology 69:219–222PubMedCrossRefGoogle Scholar
- Parkinson JA, Robbins TW, Everitt BJ (2000) Dissociable roles of the central and basolateral amygdala in appetitive emotional learning. Eur J NeuroSci 12:405–413PubMedCrossRefGoogle Scholar
- Parkinson JA, Roberts AC, Everitt BJ, Di Ciano P (2005) Acquisition of instrumental conditioned reinforcement is resistant to the devaluation of the unconditioned stimulus. Q J Exp Psychol B 58:19–30PubMedCrossRefGoogle Scholar
- Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, Academic PressGoogle Scholar
- Phillips GD, Hitchcott PK (2009) Blockade of the acquisition, but not expression, of associative learning by pre-session intra-amygdala R(+) 7-OH-DPAT. Psychopharmacology (Berl) 203:161–173CrossRefGoogle Scholar
- Phillips GD, Morutto SL (1998) Post-session sulpiride infusions within the perifornical region of the lateral hypothalamus enhance consolidation of associative learning. Psychopharmacology (Berl) 140:354–364CrossRefGoogle Scholar
- Phillips GD, Robbins TW, Everitt BJ (1994) Mesoaccumbens dopamine-opiate interactions in the control over behavior by a conditioned reinforcer. Psychopharmacology 114:345–359PubMedCrossRefGoogle Scholar
- Phillips GD, Harmer CJ, Hitchcott PK (2002a) Blockade of sensitisation-induced facilitation of appetitive conditioning by post-session intra-amygdala nafadotride. Behav Brain Res 134:249–257PubMedCrossRefGoogle Scholar
- Phillips GD, Harmer CJ, Hitchcott PK (2002b) Isolation rearing-induced facilitation of Pavlovian learning. Abolition by post-session intra-amygdala nafadotride. Physiol Behav 76:677–684PubMedCrossRefGoogle Scholar
- Phillips GD, Setzu E, Vugler A, Hitchcott PK (2003a) An immunohistochemical examination of the effects of sensitisation on the mesotelencephalic dopaminergic response to d-amphetamine. Neuroscience 117:741–753PubMedCrossRefGoogle Scholar
- Phillips GD, Setzu E, Vugler A, Hitchcott PK (2003b) Immunohistochemical assessment of mesotelencephalic dopamine activity during the acquisition and expression of Pavlovian versus instrumental behaviours. Neuroscience 117:755–767PubMedCrossRefGoogle Scholar
- Powell DA (1994) Rapid associative learning: conditioned bradycardia and its central nervous system substrates. Integr Physiol Behav Sci 29:109–133PubMedCrossRefGoogle Scholar
- Robbins TW, Everitt BJ (2007) A role for mesencephalic dopamine in activation: commentary on Berridge (2006). Psychopharmacology (Berl) 191:433–437CrossRefGoogle Scholar
- Robinson TE, Berridge KC (2003) Addiction. Annu Rev Psychol 54:25–53PubMedCrossRefGoogle Scholar
- Robinson TE, Berridge KC (2008) Review. The incentive sensitization theory of addiction: some current issues. Philos Trans R Soc Lond B Biol Sci 363:3137–3146PubMedCrossRefGoogle Scholar
- Rosenkranz JA, Grace AA (2002a) Cellular mechanisms of infralimbic and prelimbic prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala neurons in vivo. J Neurosci 22:324–337PubMedGoogle Scholar
- Rosenkranz JA, Grace AA (2002b) Dopamine-mediated modulation of odour-evoked amygdala potentials during Pavlovian conditioning. Nature 417:282–287PubMedCrossRefGoogle Scholar
- Schultz W (2002) Getting formal with dopamine and reward. Neuron 36:241–263PubMedCrossRefGoogle Scholar
- Scibilia RJ, Lachowicz JE, Kilts CD (1992) Topographic nonoverlapping distribution of D1 and D2 dopamine receptors in the amygdaloid nuclear complex of the rat brain. Synapse 11:146–154PubMedCrossRefGoogle Scholar
- Sokoloff P, Giros B, Martres MP, Andrieux M, Besancon R, Pilon C, Bouthenet ML, Souil E, Schwartz JC (1992) Localization and function of the D(3) dopamine receptor. Arzneimittel-Forschung/Drug Res 42:224–230Google Scholar
- Taylor JR, Robbins TW (1984) Enhanced behavioural control by conditioned reinforcers following microinjections of d-amphetamine into the nucleus accumbens. Psychopharmacology (Berl) 84:405–412CrossRefGoogle Scholar
- Wagner AR (1978) Expectancies and the priming of STM. In: Hulse SH, Fowler H, Hoenig WK (eds) Cognitive processes in animal behavior. Erlbaum, HillsdaleGoogle Scholar
- Wagner AR (2008) Evolution of an elemental theory of Pavlovian conditioning. Learn Behav 36:253–265PubMedCrossRefGoogle Scholar
- Wagner AR, Brandon SE (1989) Evolution of a structured connectionist model of Pavlovian conditioning (AESOP). In: Klein SB, Mowrer RR (eds) Contemporary learning theories: Pavlovian conditioning and the status of traditional learning theory. Erlbaum, Hillsdale, pp 149–189Google Scholar
- White NM, McDonald RJ (2002) Multiple parallel memory systems in the brain of the rat. Neurobiol Learn Mem 77:125–184PubMedCrossRefGoogle Scholar
- Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, McGraw-HillGoogle Scholar
- Wise RA (2006) Role of brain dopamine in food reward and reinforcement. Philos Trans R Soc Lond B Biol Sci 361:1149–1158PubMedCrossRefGoogle Scholar
- Zoli M, Torri C, Ferrari R, Jansson A, Zini I, Fuxe K, Agnati LF (1998) The emergence of the volume transmission concept. Brain Res Brain Res Rev 26:136–147PubMedCrossRefGoogle Scholar