Amphetamine-Associated Contextual Learning Is Accompanied by Structural and Functional Plasticity in the Basolateral Amygdala

被引:35
作者
Rademacher, David J. [1 ]
Rosenkranz, J. Amiel [1 ]
Morshedi, Maud M. [1 ]
Sullivan, Elyse M. [1 ]
Meredith, Gloria E. [1 ]
机构
[1] Rosalind Franklin Univ Med & Sci, Dept Cellular & Mol Pharmacol, Chicago Med Sch, N Chicago, IL 60604 USA
关键词
CONDITIONED PLACE PREFERENCE; LONG-TERM POTENTIATION; PAIRED-PULSE FACILITATION; MESSENGER-RNA EXPRESSION; NEURONS IN-VIVO; NUMERICAL DENSITY; LATERAL AMYGDALA; SYNAPTIC PLASTICITY; AXOSPINOUS SYNAPSES; CEREBELLAR CORTEX;
D O I
10.1523/JNEUROSCI.6165-09.2010
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Drug seeking and the vulnerability to relapse occur when individuals are exposed to an environment with sensory cues in which drug taking has occurred. Memory formation is thought to require plasticity in synaptic circuits, and so we examined whether the memory for a drug-paired environment correlates with changes in the synaptic circuits of the basolateral amygdala (BLA), in which emotional learning is a recognized phenomenon. We used amphetamine (AMPH) as the unconditioned stimulus in the conditioned place preference (CPP) paradigm. Rats were conditioned with 1.0 mg/kg AMPH and tested, drug free, 72 h after the last conditioning session. Controls included a saline-conditioned group and a home cage AMPH injection group, whose exposure to the CPP apparatus was delayed by 4 h, long enough to clear the AMPH from the brain. We counted excitatory synapses in the BLA using the electron microscope and the physical disector design (stereology). Rats that expressed AMPH CPP had an increase in excitatory synapses compared with controls. Excitatory synaptic activity was measured using in vivo intracellular recordings from the BLA in anesthetized rats. We found that AMPH CPP, but not drug alone, increased measures of synaptic drive, including the frequency of synaptic events, and the paired-pulse ratio of synaptic inputs to BLA pyramidal neurons. The in vivo findings suggest that the increase in BLA neuronal excitatory drive reflects the change in excitatory synapse number. Thus, context-drug associations are accompanied by structural and functional plasticity in the BLA, findings that have important implications for drug-seeking behavior.
引用
收藏
页码:4676 / 4686
页数:11
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