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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 5-AZA infusion decreases the subsequent cue-maintained cocaine seeking behaviors.(a) Schematic representation of the experimental procedure. (b) Total number of infusions across acquisition of cocaine self-administration. (c) Nose-poke responses during the reactivation trial. (d) Nose-poke responses during the conditioned reinforcement test. (e) Active (left) and inactive (right) nosepoke responses during the last day of extinction and the cocaine-priming + cue-induced reinstatement test. *Different from vehicle group, p < 0.05; **Different from vehicle group, p < 0.01.
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f4: Immediate post-reactivation intra-BLA 5-AZA infusion decreases the subsequent cue-maintained cocaine seeking behaviors.(a) Schematic representation of the experimental procedure. (b) Total number of infusions across acquisition of cocaine self-administration. (c) Nose-poke responses during the reactivation trial. (d) Nose-poke responses during the conditioned reinforcement test. (e) Active (left) and inactive (right) nosepoke responses during the last day of extinction and the cocaine-priming + cue-induced reinstatement test. *Different from vehicle group, p < 0.05; **Different from vehicle group, p < 0.01.

Mentions: We trained rats to intravenously self-administer cocaine during three 1-h daily sessions over 10 days. To test the effects of disruption of the cocaine-cue memory on the cue-maintained cocaine-seeking behavior, we omitted the nosepoke extinction sessions in this experiment. Twenty-four hours after the last cocaine self-administration session, all rats received a 15-min reactivation session induced by cocaine-associated cue reexposure. Immediately after the reactivation session, rats received bilateral intra-BLA infusion of 5-AZA or vehicle. Twenty-four hours later, all rats were tested for cue-induced reinstatement. After 5 days of daily cue extinction, rats were subsequently tested for cocaine priming-induced reinstatement (see Fig. 4a).


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 5-AZA infusion decreases the subsequent cue-maintained cocaine seeking behaviors.(a) Schematic representation of the experimental procedure. (b) Total number of infusions across acquisition of cocaine self-administration. (c) Nose-poke responses during the reactivation trial. (d) Nose-poke responses during the conditioned reinforcement test. (e) Active (left) and inactive (right) nosepoke responses during the last day of extinction and the cocaine-priming + cue-induced reinstatement test. *Different from vehicle group, p < 0.05; **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

f4: Immediate post-reactivation intra-BLA 5-AZA infusion decreases the subsequent cue-maintained cocaine seeking behaviors.(a) Schematic representation of the experimental procedure. (b) Total number of infusions across acquisition of cocaine self-administration. (c) Nose-poke responses during the reactivation trial. (d) Nose-poke responses during the conditioned reinforcement test. (e) Active (left) and inactive (right) nosepoke responses during the last day of extinction and the cocaine-priming + cue-induced reinstatement test. *Different from vehicle group, p < 0.05; **Different from vehicle group, p < 0.01.
Mentions: We trained rats to intravenously self-administer cocaine during three 1-h daily sessions over 10 days. To test the effects of disruption of the cocaine-cue memory on the cue-maintained cocaine-seeking behavior, we omitted the nosepoke extinction sessions in this experiment. Twenty-four hours after the last cocaine self-administration session, all rats received a 15-min reactivation session induced by cocaine-associated cue reexposure. Immediately after the reactivation session, rats received bilateral intra-BLA infusion of 5-AZA or vehicle. Twenty-four hours later, all rats were tested for cue-induced reinstatement. After 5 days of daily cue extinction, rats were subsequently tested for cocaine priming-induced reinstatement (see Fig. 4a).

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