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Research ArticleNew Research, Cognition and Behavior

Amygdala Dopamine Receptors Are Required for the Destabilization of a Reconsolidating Appetitive Memory

Emiliano Merlo, Patrizia Ratano, Elena C. Ilioi, Miranda A.L.S. Robbins, Barry J. Everitt and Amy L. Milton
eNeuro 18 February 2015, 2 (1) ENEURO.0024-14.2015; https://doi.org/10.1523/ENEURO.0024-14.2015
Emiliano Merlo
Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
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Patrizia Ratano
Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
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Elena C. Ilioi
Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
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Miranda A.L.S. Robbins
Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
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Barry J. Everitt
Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
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Amy L. Milton
Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
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Figures

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  • Figure 1
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    Figure 1

    Injector tips were located within the BLA for animals receiving vehicle (A), SCH23390 (B), raclopride (C), and α-flupenthixol (D) prior to memory reactivation. Circles represent animals that received vehicle following memory reactivation, and squares the placements for the animals that received anisomycin following reactivation. Distances are given from bregma. This figure was modified, with permission, from Paxinos & Watson (2004).

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    Figure 2

    Dopamine receptor antagonism had no acute effects on behavior during the memory reactivation session. There were no differences between experimental groups in the number of nosepoke responses made or the number of CSs obtained during the memory reactivation session. Thus, dopamine receptor antagonism with SCH23390 (SCH), raclopride (RAC), or α-flupenthixol (FLU) did not acutely affect activity or memory retrieval relative to vehicle (VEH). Data are presented as means ± SEM. The bars represent data for all animals receiving the same infusion prior to reactivation; the circles and triangles represent data for the prospective experimental groups, based on the second infusion of anisomycin or vehicle following the reactivation session. Group sizes: VEH/VEH = 26; VEH/ANI = 9; SCH/VEH = 8; SCH/ANI = 6; RAC/VEH = 8; RAC/ANI = 7; FLU/VEH = 5; FLU/ANI = 8 rats per group.

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    Figure 3

    D1- or D2-subtype-selective dopamine receptor antagonism prevented the destabilization of CS−sucrose memory. A, The protein synthesis inhibitor anisomycin (ANI), given immediately after CS−sucrose memory reactivation, disrupted memory reconsolidation when it followed an intra-BLA vehicle (VEH) infusion prior to reactivation, consequently preventing the CS from acting as a conditioned reinforcer during the test sessions. B, C, Antagonism at D1 dopamine receptors with SCH23390 (SCH; B) or antagonism at D2 dopamine receptors with raclopride (RAC; C) prior to reactivation prevented the amnestic effect of ANI, allowing the CS to act as a conditioned reinforcer during testing, consistent with a blockade of memory destabilization. D, Nonselective antagonism at dopamine receptors with α-flupenthixol (FLU) prior to reactivation did not prevent the amnestic effect of ANI administered post-reactivation. Data are square-root transformed and shown as mean ± SEM. Group sizes are as in Figure 2, with the same animals tested in each session.

Tables

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    Table 1

    Statistics

    AnalysisEffectOutcomeData structureType of testPower (α = 0.05)
    NP at TRsquadF(17,59) = 1.15a20.681
    sessionF(6.1,421) = 13.0a11
    session × drug1F(18,421) = 1.59a10.935
    session × drug2F(6.1,421) = 1.25a10.499
    session × drug1 × drug2F < 1a10.617
    drug1F < 1a10.089
    drug2F < 1a10.052
    drug1 × drug2F < 1a10.096
    CS at TRsessionF(8,552) = 1.20b10.559
    drug1F < 1b10.234
    drug2F(1,69) = 2.52b10.346
    drug1 × drug2F < 1b10.234
    session × drug1F(24,552) = 1.56b10.971
    session x drug1 x drug2F(24,552) = 1.56b10.971
    NP at ReactsquadF(17,59) = 1.54b20.836
    drug1F < 1b20.159
    CS at Reactdrug1F(3,76) = 1.45b20.37
    NP at Reactdrug2F < 1b30.077
    drug1 × drug2F < 1b30.146
    CS at Reactdrug2F < 1b30.086
    drug1 × drug2F < 1b30.156
    LP at ANRsquadF(17,59) = 1.08a20.644
    drug1 × drug2F(3,69) = 3.40a10.743
    lever × drug1 × drug2F(38.4,69.0) = 3.11a10.701
    drug1F(3,69) = 1.24a10.319
    lever × drug1F(14.4,69.0) = 1.16a10.3
    drug2F(1,69) = 2.67a10.364
    lever × drug2F < 1a10.052
    NP at ANRdrug1F < 1a10.116
    drug2F(1,69) = 1.44a10.212
    drug1 × drug2F(3,69) = 1.72a10.498
    session × drug1F(16.7,386) = 1.71a10.941
    LP/VEHANIF(1,33) = 5.33a10.61
    lever × session in VEH/VEHF(3.6,89.6) = 6.27a10.978
    lever × session in VEH/ANIF(2.4,19.4) = 1.8a10.36
    NP/VEHANIF(1,33) = 2.05a10.285
    session × ANIF < 1a10.265
    LP/SCHSCH × ANIF(1,45) = 6.75a10.720
    ANIF < 1a10.131
    lever × ANIF < 1a10.078
    lever × session × ANIF(2.99,35.9) = 1.60a10.384
    leverF(1,12) = 36.7a11
    lever × sessionF(2.99,35.9) = 3.88a10.78
    NP/SCHANIF(1,12) = 1.55a10.209
    session × ANIF < 1a10.124
    LP/RACRAC × ANIF(1,46) = 7.26a10.751
    leverF(1,13) = 23.1a10.993
    lever × ANIF(1,13) = 6.04a10.623
    ANIF < 1a10.081
    NP/RACANIF(1,13) = 2.64a10.324
    session × ANIF < 1a10.319
    LP/FLUFLU × ANIF(1,44) = 2.26a10.312
    ANIF(1,11) = 7.48a10.702
    NP/FLUANIF(1,11) = 1.36a10.187
    session × ANIF < 1a10.231
    LP/Drug1drug1F < 1a10.249
    lever × drug1F(3,43) = 1.43a10.352
    session × drug1F(15.6,224) = 1.11a10.72
    lever × session × drug1F < 1a10.5
    LP/ANIdrug1F(3,26) = 3.01a10.639
    lever × drug1F(3,26) = 2.53a10.557
    VEH/ANIleverF(1,8) = 2.13a10.251
    FLU/ANIleverF(1,7) = 3.06a10.327
    SCH/ANIleverF(1,5) = 29.6a10.989
    RAC/ANIleverF(1,6) = 39.6a10.999
    • a, Normal distribution after transformation; b, normal distribution; 1, repeated-measures ANOVA; 2, one-way ANOVA; 3, two-way ANOVA. NP, nosepoke; TR, training session; React, memory reactivation session; LP, lever pressing; ANR, acquisition of a new response.

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    Table 2

    Training performance was equivalent across experimental groups Data are presented as mean ± SEM and where appropriate are given to 3 significant figures

    Session123456789
    CSs
    VEH/VEH30 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 0
    VEH/ANI30 ± 030 ± 030 ± 030 ± 030 ± 029.7 ± 0.3330 ± 030 ± 030 ± 0
    SCH/VEH30 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 0
    SCH/ANI30 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 0
    RAC/VEH30 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 0
    RAC/ANI30 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 029.4 ± 0.57
    FLU/VEH30 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 0
    FLU/ANI30 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 030 ± 0
    Nosepokes
    VEH/VEH80.2 ± 2.3770.5 ± 2.6764.8 ± 2.3360.4 ± 2.4762.8 ± 2.9566.5 ± 3.0672.8 ± 5.3372.2 ± 4.2882.3 ± 5.66
    VEH/ANI86.6 ± 7.0165.3 ± 3.5462.2 ± 4.1662.3 ± 3.7261.0 ± 2.8663.9 ± 6.3872.6 ± 4.3670.7 ± 6.2679.9 ± 6.75
    SCH/VEH85.5 ± 7.5380.1 ± 10.872.0 ± 8.7969.6 ± 11.477.0 ± 16.081.5 ± 16.577.8 ± 11.768.9 ± 12.370.1 ± 9.76
    SCH/ANI88.5 ± 7.4880.7 ± 5.4465.7 ± 4.5570.8 ± 2.0972.8 ± 6.5273.0 ± 6.9669.0 ± 6.5257.5 ± 4.1685.3 ± 8.09
    RAC/VEH82.5 ± 4.1573.3 ± 4.8571.8 ± 7.5674.5 ± 5.6160.5 ± 6.0469.6 ± 3.6765.1 ± 4.6766.0 ± 6.3977.8 ± 7.41
    RAC/ANI79.3 ± 3.5773.6 ± 5.5567.0 ± 2.2763.9 ± 1.7158.7 ± 3.9457.3 ± 3.4159.9 ± 7.4873.1 ± 12.881.1 ± 16.6
    FLU/VEH79.6 ± 8.5973.4 ± 13.5368.2 ± 7.8664.0 ± 7.5658.0 ± 8.1365.6 ± 5.4563.4 ± 9.6982.0 ± 7.5067.6 ± 8.33
    FLU/ANI84.6 ± 5.7364.8 ± 4.0573.3 ± 6.5267.4 ± 5.9363.4 ± 6.6764.0 ± 3.4969.0 ± 5.1566.5 ± 4.9884.3 ± 7.44
    • View popup
    Table 3

    Nosepokes made during testing of the acquisition of a new instrumental response for conditioned reinforcement. Data are presented as mean ± s.e.m. and are given to 3sf.

    Post-reactivation day1258152229
    VEH/VEH54.1 ± 5.7952.2 ± 5.6047.5 ± 3.9549.8 ± 3.9856.9 ± 3.6545.2 ± 3.9938.3 ± 3.05
    VEH/ANI39.3 ± 6.0742.9 ± 6.9240.3 ± 5.2144.9 ± 5.9836.6 ± 4.9238.9 ± 4.8236.7 ± 6.26
    SCH/VEH61.1 ± 11.543.0 ± 4.3039.5 ± 4.9950.5 ± 8.8238.5 ± 3.5848.8 ± 13.437.6 ± 8.21
    SCH/ANI43.0 ± 9.4935.3 ± 5.1233.2 ± 4.9033.8 ± 4.4435.0 ± 5.6532.3 ± 5.8229.8 ± 6.40
    RAC/VEH33.1 ± 4.9832.6 ± 4.5736.5 ± 5.5439.4 ± 4.8550.8 ± 4.6342.0 ± 5.0440.5 ± 4.56
    RAC/ANI39.3 ± 6.4744.9 ± 12.547.4 ± 9.3666.4 ± 9.7255.3 ± 5.5656.3 ± 9.9643.3 ± 6.75
    FLU/VEH45.7 ± 8.7340.2 ± 5.5450.0 ± 8.1145.2 ± 8.2768.0 ± 23.743.2 ± 5.1754.2 ± 8.36
    FLU/ANI48.4 ± 11.033.6 ± 4.4540.0 ± 6.7533.4 ± 2.9035.6 ± 4.9247.3 ± 11.142.9 ± 7.57
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Amygdala Dopamine Receptors Are Required for the Destabilization of a Reconsolidating Appetitive Memory
Emiliano Merlo, Patrizia Ratano, Elena C. Ilioi, Miranda A.L.S. Robbins, Barry J. Everitt, Amy L. Milton
eNeuro 18 February 2015, 2 (1) ENEURO.0024-14.2015; DOI: 10.1523/ENEURO.0024-14.2015

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Amygdala Dopamine Receptors Are Required for the Destabilization of a Reconsolidating Appetitive Memory
Emiliano Merlo, Patrizia Ratano, Elena C. Ilioi, Miranda A.L.S. Robbins, Barry J. Everitt, Amy L. Milton
eNeuro 18 February 2015, 2 (1) ENEURO.0024-14.2015; DOI: 10.1523/ENEURO.0024-14.2015
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