Temporally graded, context-specific retrograde amnesia and its alleviation by context preexposure: Effects of postconditioning exposures to morphine in the rat.

McNally, Gavan P.; Westbrook, R. Frederick

doi:10.1037/0097-7403.29.2.130

Cited by 19 publications

(19 citation statements)

References 57 publications

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“…Rats that have had an adrenalectomy, or hippocampal lesions, or that experience post-conditioning social isolation stress, morphine injections or bacterial lipopolysaccharide-induced inflammation show reduced CX- but not CS-fear. However, pre-exposing the rats to the context prior to conditioning can prevent these effects [35–37,51,52]. Similarly, rats that have had long periods of time to explore the context prior to the shock (say, 120 s) show greater CX-fear conditioning than rats that are shocked shortly after being placed in the context (<27 s).…”

Section: Discussionmentioning

confidence: 99%

“…Immediate post-conditioning injection of morphine [34], bacterial lipopolysaccharides [37] or live Escherischia coli [74], intracerebral infusions with proinflammatory cytokines [56] all specifically reduce context fear conditioning. In addition, context conditioning can also be reduced by experience with psychological stressors, such as social isolation, after conditioning [36] or by the chronic administration of opioids beginning days after conditioning [35]. …”

Section: Discussionmentioning

confidence: 99%

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Post-conditioning experience with acute or chronic inflammatory pain reduces contextual fear conditioning in the rat

Johnston

Maier

Rudy

et al. 2012

Behavioural Brain Research

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There is evidence that pain can impact cognitive function in people. The present study evaluated whether Pavlovian fear conditioning in rats would be reduced if conditioning were followed by persistent inflammatory pain induced by a subcutaneous injection of dilute formalin or complete Freund's adjuvant (CFA) on the dorsal lumbar surface of the back. Formalin-induced pain specifically impaired contextual fear conditioning but not auditory cue conditioning (Experiment 1A). Moreover, formalin pain only impaired contextual fear conditioning if it was initiated within 1 h of conditioning and did not have a significant effect if initiated 2, 8 or 32 h after (Experiments 1A and 1B). Experiment 2 showed that formalin pain initiated after a session of context pre-exposure reduced the ability of that pre-exposure to facilitate contextual fear when the rat was limited to a brief exposure to the context during conditioning. Similar impairments in context- but not CS-fear conditioning were also observed if the rats received an immediate post-conditioning injection with CFA (Experiment 3). Finally, we confirmed that formalin and CFA injected s.c. on the back induced pain-indicative behaviours, hyperalgesia and allodynia with a similar timecourse to intraplantar injections (Experiment 4). These results suggest that persistent pain impairs learning in a hippocampus-dependent task, and may disrupt processes that encode experiences into long-term memory.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Post-conditioning experience with acute or chronic inflammatory pain reduces contextual fear conditioning in the rat

Johnston

Maier

Rudy

et al. 2012

Behavioural Brain Research

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“…The endogenous opioid system may be involved in erasure of conditioned fear during extinction in P17 rats because there is evidence showing that the activation of opioid system disrupts consolidation of memory in adult rats. For example, postconditioning injections of opioid receptor agonists disrupt long-term memory (e.g., Rudy et al 1999;McNally and Westbrook 2003b). Therefore, increased opioid neurotransmission triggered by extinction training may cause some unlearning of the fear memory.…”

Section: Extinction Of Conditioned Fear In the Developing Ratmentioning

confidence: 99%

The effect of the μ-opioid receptor antagonist naloxone on extinction of conditioned fear in the developing rat

Kim

Richardson²

2009

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Several recent studies report that neurotransmitters that are critically involved in extinction in adult rats are not important for extinction in young rats. Specifically, pretest injection of the g-aminobutryic acid (GABA) receptor inverse agonist FG7142 has no effect on extinction in postnatal day (P)17 rats, although it reverses extinction in P24 rats as reported by Kim and Richardson in an earlier paper. Further, pre-extinction injection of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 has no effect on extinction in P17 rats, whereas it impairs long-term extinction in P24 rats as per Langton and colleagues in an earlier work. These findings indicate that extinction in P17 rats is qualitatively different from extinction in older rats. The present study examines the involvement of the endogenous opioid system in extinction in the developing rat using systemic injections of the m-opioid receptor antagonist naloxone. Experiment 1 showed that injection of naloxone before extinction training disrupted the acquisition of extinction in both P17 and P24 rats. This effect was dependent on central rather than peripheral m-opioid receptors (Experiment 2), and neither pre-test nor post-extinction injection of naloxone had effects on extinction (Experiments 3 and 4). Taken together, these findings indicate that opioid neurotransmission, in contrast to GABA and NMDA activity, is critical for extinction acquisition across development.Pavlovian conditioned fear is typically acquired by pairing an initially neutral conditioned stimulus (CS; e.g., tone) with an aversive unconditioned stimulus (US; e.g., shock). The formation of an association between the CS and the US is inferred when subsequent presentations of the CS elicits various conditioned fear responses (CR; e.g., freezing). These learned fear responses can subsequently be reduced by giving nonreinforced presentations of the CS-a process referred to as extinction. Fear extinction has received considerable attention over the past decade because of its theoretical importance and its obvious clinical implications for the treatment of various anxiety disorders (Davis and Myers 2002). Early models of associative learning suggested that extinction was due to the ''unlearning'' or ''erasure'' of the original CS-US association (e.g., Rescorla and Wagner 1972). However, it is now more widely accepted that the reduced CR following extinction reflects new learning of a CS-no US association that inhibits the expression of the original CS-US association (e.g., Bouton 2002). The primary evidence for this view comes from behavioral studies that show performance to an extinguished CS can recover without any retraining (e.g., spontaneous recovery, renewal, and reinstatement). Additionally, we know that extinction involves inhibition because reducing g-amino butyric acid (GABA) inhibitory activity by pretest injections of the GABA receptor inverse agonist FG7142 reverses extinction (Harris and Westbrook 1998). Finally, preextinction injection of the N-methyl-D-aspartate (NM...

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“…However, as neither NMDA or GABA seem to be involved in extinction in PND 16 rats (present results; Kim and Richardson 2007a), one potential mechanism for extinction in young rats is the endogenous opioid system. This neurotransmitter system has been found to regulate fear conditioning (McNally and Westbrook 2003) and extinction (McNally et al 2004) in adult rats. Moreover, the opioid system is a likely mechanism for mediating extinction in young rats, as it is active from birth (Blass et al 1991) and has been found to modulate memory in infant rats (Weber et al 2006).…”

Section: Org Downloaded Frommentioning

confidence: 99%

The effect of the NMDA receptor antagonist MK-801 on the acquisition and extinction of learned fear in the developing rat

Langton

Kim²,

Nicholas³

et al. 2007

Learn. Mem.

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Recent findings reveal qualitative developmental differences in extinction of learned fear. The present study explored potential developmental differences in the role of NMDA in acquisition and extinction. Rats were injected with MK-801 prior to fear conditioning or extinction training. Acquisition was found to be NMDA dependent in both age groups, whereas extinction was found to be NMDA dependent in 23-day-old rats, but NMDA independent in 16-day-old rats. These results illustrate another fundamental developmental difference in extinction as well as a dissociation in the role of NMDA in the acquisition and extinction of fear early in development.The acquisition of fear is commonly studied with Pavlovian conditioning procedures in which a neutral conditioned stimulus (CS; e.g., tone) is paired with an aversive unconditioned stimulus (US; e.g., footshock). Subsequent presentations of the CS elicit a number of fear responses (e.g., freezing), but these reactions can be extinguished by repeatedly presenting the CS in the absence of the US. Previous research shows that both the acquisition and extinction of learned fear involves N-methyl-D-aspartate (NMDA) receptors. Specifically, infusing APV (a selective NMDA antagonist) into the amygdala impairs acquisition of fear conditioning (Miserendino et al. 1990) and extinction (Falls et al. 1992). Baker and Azorlosa (1996) also found that NMDA antagonists impair long-term extinction by giving systemic injections of MK-801.While NMDA is involved in both the acquisition and extinction of learned fear in adult rats, the role of NMDA in these processes has not been systematically examined during development. Further, recent studies suggest that the mechanisms underlying extinction are qualitatively different during development. More specifically, renewal and reinstatement are observed in adult rats (see Bouton 2002) and postnatal day (PND) 23 rats; however, neither occur in PND 16 rats (Kim and Richardson 2007a,b;Yap and Richardson 2007). Likewise, pre-test administration of the GABA inverse agonist FG-7142 results in a return of conditioned responding after extinction training in PND 23 (Kim and Richardson 2007a) and adult rats (Harris and Westbrook 1998), but not in PND 16 rats. Taken together, these findings provide support for the idea that the processes mediating extinction are not uniform across development.This study explored developmental differences in the role of NMDA in the acquisition and extinction of learned fear. Specifically, the effect of the NMDA receptor antagonist MK-801 on fear conditioning and extinction was examined in PND 16 and PND 23 rats. In each experiment, the group label refers to the age at which fear conditioning occurred.The fear conditioning and extinction procedures used in the current study were the same as previous studies from our laboratory (see Kim and Richardson 2007a for details). MK-801 (Sigma-Aldrich) or saline was administered subcutaneously at a volume of 2 mL/kg. First, we examined whether there are age-related differences in th...

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Temporally graded, context-specific retrograde amnesia and its alleviation by context preexposure: Effects of postconditioning exposures to morphine in the rat.

Cited by 19 publications

References 57 publications

Post-conditioning experience with acute or chronic inflammatory pain reduces contextual fear conditioning in the rat

Post-conditioning experience with acute or chronic inflammatory pain reduces contextual fear conditioning in the rat

The effect of the μ-opioid receptor antagonist naloxone on extinction of conditioned fear in the developing rat

The effect of the NMDA receptor antagonist MK-801 on the acquisition and extinction of learned fear in the developing rat

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