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Reconsolidation of a cocaine associated memory requires DNA methyltransferase activity in the basolateral amygdala.

Shi HS, Luo YX, Yin X, Wu HH, Xue G, Geng XH, Hou YN - Sci Rep (2015)

Bottom Line: Bilateral intra-basolateral amygdala (BLA) infusion of the DNMT inhibitor5-azacytidine (5-AZA, 1 μg per side) immediately following reactivation decreased subsequent reinstatement induced by cues or cocaine priming as well as cue-maintained cocaine-seeking behaviour.In contrast, delayed intra-BLA infusion of 5-AZA 6 h after reactivation or 5-AZA infusion without reactivation had no effect on subsequent cue-induced reinstatement.These findings indicate that memory reconsolidation for a cocaine-paired stimulus depends critically on DNMT activity in the BLA.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.

ABSTRACT
Drug addiction is considered an aberrant form of learning, and drug-associated memories evoked by the presence of associated stimuli (drug context or drug-related cues) contribute to recurrent craving and reinstatement. Epigenetic changes mediated by DNA methyltransferase (DNMT) have been implicated in the reconsolidation of fear memory. Here, we investigated the role of DNMT activity in the reconsolidation of cocaine-associated memories. Rats were trained over 10 days to intravenously self-administer cocaine by nosepokes. Each injection was paired with a light/tone conditioned stimulus (CS). After acquisition of stable self-administration behaviour, rats underwent nosepoke extinction (10 d) followed by cue-induced reactivation and subsequent cue-induced and cocaine-priming + cue-induced reinstatement tests or subsequently tested to assess the strength of the cocaine-associated cue as a conditioned reinforcer to drive cocaine seeking behaviour. Bilateral intra-basolateral amygdala (BLA) infusion of the DNMT inhibitor5-azacytidine (5-AZA, 1 μg per side) immediately following reactivation decreased subsequent reinstatement induced by cues or cocaine priming as well as cue-maintained cocaine-seeking behaviour. In contrast, delayed intra-BLA infusion of 5-AZA 6 h after reactivation or 5-AZA infusion without reactivation had no effect on subsequent cue-induced reinstatement. These findings indicate that memory reconsolidation for a cocaine-paired stimulus depends critically on DNMT activity in the BLA.

No MeSH data available.


Related in: MedlinePlus

Immediate post-reactivation intra-BLA DNMT inhibition reduces subsequent cue-induced and cocaine-priming + cue-induced reinstatement.(a) Schematic representation of the experimental procedure. (b) Photomicrographs of representative cannula placements in BLA. (c) Total number of cocaine infusions across acquisition of cocaine self-administration sessions. (d) Total number of active nosepoke responses across nosepoke response extinction. (e) Nosepoke responses during reactivation trial. (f) Active (left) and inactive (right) nosepoke responses during the last extinction session of the nosepoke extinction sessions and the cue-induced reinstatement test. (g) Active (left) and inactive (right) nosepoke responses during the last extinction of the cue extinction sessions and the cocaine-priming + cue-induced reinstatement test. **Different from vehicle group, p < 0.01.
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f1: Immediate post-reactivation intra-BLA DNMT inhibition reduces subsequent cue-induced and cocaine-priming + cue-induced reinstatement.(a) Schematic representation of the experimental procedure. (b) Photomicrographs of representative cannula placements in BLA. (c) Total number of cocaine infusions across acquisition of cocaine self-administration sessions. (d) Total number of active nosepoke responses across nosepoke response extinction. (e) Nosepoke responses during reactivation trial. (f) Active (left) and inactive (right) nosepoke responses during the last extinction session of the nosepoke extinction sessions and the cue-induced reinstatement test. (g) Active (left) and inactive (right) nosepoke responses during the last extinction of the cue extinction sessions and the cocaine-priming + cue-induced reinstatement test. **Different from vehicle group, p < 0.01.

Mentions: Histological slides were obtained from the experimental subjects. After behavioral tests were completed, all of the rats were anesthetized with sodium pentobarbital (100 mg/kg, i.p.) and transcardially perfused with paraformaldehyde. Cannula placements were assessed by Nissl’s staining of 40-μm thick coronal sections and examination under light microscopy2435. The locations of representative cannula tips are shown in Fig. 1b.


Reconsolidation of a cocaine associated memory requires DNA methyltransferase activity in the basolateral amygdala.

Shi HS, Luo YX, Yin X, Wu HH, Xue G, Geng XH, Hou YN - Sci Rep (2015)

Immediate post-reactivation intra-BLA DNMT inhibition reduces subsequent cue-induced and cocaine-priming + cue-induced reinstatement.(a) Schematic representation of the experimental procedure. (b) Photomicrographs of representative cannula placements in BLA. (c) Total number of cocaine infusions across acquisition of cocaine self-administration sessions. (d) Total number of active nosepoke responses across nosepoke response extinction. (e) Nosepoke responses during reactivation trial. (f) Active (left) and inactive (right) nosepoke responses during the last extinction session of the nosepoke extinction sessions and the cue-induced reinstatement test. (g) Active (left) and inactive (right) nosepoke responses during the last extinction of the cue extinction sessions and the cocaine-priming + cue-induced reinstatement test. **Different from vehicle group, p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542613&req=5

f1: Immediate post-reactivation intra-BLA DNMT inhibition reduces subsequent cue-induced and cocaine-priming + cue-induced reinstatement.(a) Schematic representation of the experimental procedure. (b) Photomicrographs of representative cannula placements in BLA. (c) Total number of cocaine infusions across acquisition of cocaine self-administration sessions. (d) Total number of active nosepoke responses across nosepoke response extinction. (e) Nosepoke responses during reactivation trial. (f) Active (left) and inactive (right) nosepoke responses during the last extinction session of the nosepoke extinction sessions and the cue-induced reinstatement test. (g) Active (left) and inactive (right) nosepoke responses during the last extinction of the cue extinction sessions and the cocaine-priming + cue-induced reinstatement test. **Different from vehicle group, p < 0.01.
Mentions: Histological slides were obtained from the experimental subjects. After behavioral tests were completed, all of the rats were anesthetized with sodium pentobarbital (100 mg/kg, i.p.) and transcardially perfused with paraformaldehyde. Cannula placements were assessed by Nissl’s staining of 40-μm thick coronal sections and examination under light microscopy2435. The locations of representative cannula tips are shown in Fig. 1b.

Bottom Line: Bilateral intra-basolateral amygdala (BLA) infusion of the DNMT inhibitor5-azacytidine (5-AZA, 1 μg per side) immediately following reactivation decreased subsequent reinstatement induced by cues or cocaine priming as well as cue-maintained cocaine-seeking behaviour.In contrast, delayed intra-BLA infusion of 5-AZA 6 h after reactivation or 5-AZA infusion without reactivation had no effect on subsequent cue-induced reinstatement.These findings indicate that memory reconsolidation for a cocaine-paired stimulus depends critically on DNMT activity in the BLA.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Bethune International Peace Hospital of PLA, Shijiazhuang 050082, China.

ABSTRACT
Drug addiction is considered an aberrant form of learning, and drug-associated memories evoked by the presence of associated stimuli (drug context or drug-related cues) contribute to recurrent craving and reinstatement. Epigenetic changes mediated by DNA methyltransferase (DNMT) have been implicated in the reconsolidation of fear memory. Here, we investigated the role of DNMT activity in the reconsolidation of cocaine-associated memories. Rats were trained over 10 days to intravenously self-administer cocaine by nosepokes. Each injection was paired with a light/tone conditioned stimulus (CS). After acquisition of stable self-administration behaviour, rats underwent nosepoke extinction (10 d) followed by cue-induced reactivation and subsequent cue-induced and cocaine-priming + cue-induced reinstatement tests or subsequently tested to assess the strength of the cocaine-associated cue as a conditioned reinforcer to drive cocaine seeking behaviour. Bilateral intra-basolateral amygdala (BLA) infusion of the DNMT inhibitor5-azacytidine (5-AZA, 1 μg per side) immediately following reactivation decreased subsequent reinstatement induced by cues or cocaine priming as well as cue-maintained cocaine-seeking behaviour. In contrast, delayed intra-BLA infusion of 5-AZA 6 h after reactivation or 5-AZA infusion without reactivation had no effect on subsequent cue-induced reinstatement. These findings indicate that memory reconsolidation for a cocaine-paired stimulus depends critically on DNMT activity in the BLA.

No MeSH data available.


Related in: MedlinePlus