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Highlights: [•] The medial prefrontal cortex is required for spatial memory extinction. [•] The amygdala complex was activated after spatial memory extinction. [•] The lateral mammillary nucleus is involved in spatial memory extinction. [ABSTRACT FROM AUTHOR]

Highlights: [•] C57BL/6 mice acquired conditioned fear and subsequent fear extinction that were retained weeks later. [•] During retention testing, dendritic spines and intersections were measured in basolateral amygdala neurons. [•] Fear conditioning increased spines and intersections and fear extinction reversed these effects. [ABSTRACT FROM AUTHOR]

Background: Like fear conditioning, the acquisition phase of extinction involves new learning that is mediated by the amygdala. During extinction training, the conditioned stimulus is repeatedly presented in the absence of the unconditioned stimulus, and the expression of previously learned fear gradually becomes suppressed. Our previous study revealed that chronic treatment with a selective serotonin reuptake inhibitor (SSRI) impairs the acquisition of auditory fear conditioning. To gain further insight into how SSRIs affect fear learning, we tested the effects of chronic SSRI treatment on the acquisition of extinction. Methods: Rats were treated chronically (22 days) or subchronically (9 days) with the SSRI citalopram (10 mg/kg/day) before extinction training. The results were compared with those after chronic and subchronic treatment with tianeptine (10 mg/kg/day), an antidepressant with a different method of action. The expression of the NR2B subunit of the N-methyl-D-aspartate receptor in the amygdala was examined after behavioral testing. Results: Chronic but not subchronic administration of citalopram impaired the acquisition of extinction and downregulated the NR2B subunit of the N-methyl-D-aspartate receptor in the lateral and basal nuclei of the amygdala. Similar behavioral and molecular changes were found with tianeptine treatment. Conclusions: These results provide further evidence that chronic antidepressant treatment can impair amygdala-dependent learning. Our findings are consistent with a role for glutamatergic neurotransmission in the final common pathway of antidepressant treatment. [ABSTRACT FROM AUTHOR]

Abstract: Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is differentially involved in these processes. [Copyright &y& Elsevier]

Research with adult animals suggests that extinction depends, at least partly, on new inhibitory learning that is specific to the context in which it is learned. However, several recent studies show that extinction processes are dissociated across development. The present article reviews research on the behavioral and neurobiological mechanisms underlying extinction in developing rats. To summarize, postweanling aged rats (i.e., 24-day-olds) display adult-like extinction in that they show renewal, reinstatement, spontaneous recovery, and compound summation of extinguished stimuli. However, preweanling aged rats (i.e., 17-day-olds) do not show any of those behavioral phenomena. Pharmacological studies also show that reducing N-methyl-D-aspartate, γ-aminobutryic acid, and opioid neurotransmission impairs extinction in 24-day-old rats, but extinction in P17 rats is only affected by the blocking of opioid neurotransmission. Lastly, extinction in 24-day-old rats involves the amygdala and the ventromedial prefrontal cortex (vmPFC), which are critical brain areas in the neural circuitry of extinction in adult rats. Interestingly, extinction in 17-day-old rats involves the amygdala but not the vmPFC. The existing models of extinction cannot account for these developmental differences. These findings showing that distinct processes mediate extinction at different stages of development may have significant clinical implications, which are discussed in this review. [Copyright &y& Elsevier]