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Opiate exposure state controls dopamine D3 receptor and cdk5/calcineurin signaling in the basolateral amygdala during reward and withdrawal aversion memory formation
被引：16
|作者：
Rosen, Laura G.
[1
,2
]
Rushlow, Walter J.
[1
,2
,3
]
Laviolette, Steven R.
[1
,2
,3
,4
]
机构：
[1] Univ Western Ontario, Schulich Sch Med & Dent, Addict Res Grp, London, ON N6A 5C1, Canada
[2] Univ Western Ontario, Schulich Sch Med & Dent, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada
[3] Univ Western Ontario, Schulich Sch Med & Dent, Dept Psychiat, London, ON N6A 5C1, Canada
[4] Univ Western Ontario, Schulich Sch Med & Dent, Dept Psychol, London, ON N6A 5C1, Canada
基金：
加拿大自然科学与工程研究理事会;
加拿大健康研究院;
关键词：
Aversion;
Basolateral amygdala;
Dopamine;
Memory;
Reward;
Withdrawal;
VENTRAL TEGMENTAL AREA;
POSITRON-EMISSION-TOMOGRAPHY;
CUE-INDUCED REINSTATEMENT;
HUMAN COCAINE FATALITIES;
D-3;
RECEPTOR;
NUCLEUS-ACCUMBENS;
SYNAPTIC PLASTICITY;
PRELIMBIC CORTEX;
UP-REGULATION;
BRAIN REWARD;
D O I：
10.1016/j.pnpbp.2017.06.009
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
The dopamine (DA) D3 receptor (D3R) is highly expressed in the basolateral nucleus of the amygdala (BLA), a neural region critical for processing opiate-related reward and withdrawal aversion-related memories. Functionally, D3R transmission is linked to downstream Cdk5 and calcineurin signaling, both of which regulate D3R activity states and play critical roles in memory-related synaptic plasticity. Previous evidence links D3R transmission to opiate-related memory processing, however little is known regarding how chronic opiate exposure may alter D3R-dependent memory mechanisms. Using conditioned place preference (CPP) and withdrawal aversion (conditioned place aversion; CPA) procedures in rats, combined with molecular analyses of BLA protein expression, we examined the effects of chronic opiate exposure on the functional role of intra-BLA D3R transmission during the acquisition of opiate reward or withdrawal aversion memories. Remarkably, we report that the state of opiate exposure during behavioural conditioning (opiate-naive/non-dependent vs. chronically exposed and in withdrawal) controlled the functional role of intra-BLA D3R transmission during the acquisition of both opiate reward memories and withdrawal-aversion associative memories. Thus, whereas intra-BLA D3R blockade had no effect on opiate reward memory formation in the non-dependent state, blockade of intra-BLA D3R transmission prevented the formation of opiate reward and withdrawal aversion memory in the chronically exposed state. This switch in the functional role of D3R transmission corresponded to significant increases in Cdk5 phosphorylation and total expression levels of calcineurin, and a corresponding decrease in intra-BLA D3R expression. Inhibition of either intra-BLA Cdk5 or calcineurin reversed these effects, switching intra-BLA associative memory formation back to a D3R-independent mechanism.
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页码：59 / 66
页数：8
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