Effects of a microinjection of morphine into the amygdala on the acquisition and expression of conditioned fear and hypoalgesia in rats.

Good, Anthony J.; Westbrook, R. Frederick

doi:10.1037/0735-7044.109.4.631

Cited by 91 publications

(68 citation statements)

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“…Although previous studies have shown that acute microinjection of morphine into the amygdala or nucleus accumbens impairs the acquisition and expression of fear memory [25,26] , little is known about the effect of chronic morphine on fear memory. We found that morphine withdrawal in mice did not affect the acquisition of contextual or cued fear responses, but inhibited the extinction of the cued fear response.…”

Section: Discussionmentioning

confidence: 99%

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

et al. 2010

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Aim: Histamine plays an important role in morphine addiction and memory-dependent behavior. However, little is known about the effect of histamine on the impairment of memory after morphine withdrawal. This study was designed to investigate the effect of histamine on memory impairment induced by morphine withdrawal in histidine decarboxylase knockout (HDC-KO) and wild-type (WT) mice. Methods: WT and HDC-KO mice were given subcutaneous morphine or saline twice daily for 5 consecutive days. The mice received a cued or contextual fear conditioning session 7 days after the last injection. During subsequent days, mice received 4 cued or contextual extinction sessions (one session per day). Western blot was used to assess extracellular signal-regulated kinase (ERK) phosphorylation in the amygdala and hippocampus. Results: Morphine withdrawal did not affect the acquisition of cued or contextual fear responses. It impaired cued but not contextual fear extinction. The acquisition of cued and contextual fear responses was accelerated in HDC-KO mice. Histamine deficiency aggravated the impairment of cued fear extinction induced by morphine withdrawal, whereas histamine (icv, 5 µg/mouse) reversed this effect. Morphine withdrawal decreased ERK phosphorylation in the amygdala after cued fear extinction, especially in HDC-KO mice. Conclusion: These results suggest that morphine withdrawal specifically impairs cued fear extinction and histamine ameliorates this impairment. Its action might be mediated by the modulation of ERK phosphorylation in the amygdala. Histamine should be explored for possible roles in the prevention or treatment of morphine abuse and relapse.

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Section: Discussionmentioning

confidence: 99%

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

et al. 2010

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“…The right vlPAG was targeted so that the tip of the guide cannula was positioned 5.6 mm below lambda through a hole drilled 0.1 mm anterior to and 0.8 mm lateral to lambda. We implanted cannula into only one hemisphere for two reasons: First, to reduce the possible extent of damage to the PAG and overlying blood vessels; second, because previous research has demonstrated that a unilateral manipulation was sufficient to observe an effect on fear conditioning in a number of brain regions critical for this learning (for example, see Good and Westbrook 1995;LaBar and LeDoux 1996;McNally and Cole 2006). We chose the right PAG to facilitate comparison with our previous experiments (McNally and Cole 2006).…”

Section: Surgery and Histologymentioning

confidence: 99%

Opioid receptors mediate direct predictive fear learning: Evidence from one-trial blocking

Cole¹,

McNally²

2007

Learn. Mem.

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Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including µ-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear learning. Four experiments reported here used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct or indirect action of predictive error on Pavlovian association formation. In Stage I, rats were trained to fear conditioned stimulus (CS) A by pairing it with shock. In Stage II, CSA and CSB were co-presented once and co-terminated with shock. Two novel stimuli, CSC and CSD, were also co-presented once and co-terminated with shock in Stage II. The results showed one-trial blocking of fear learning (Experiment 1) as well as one-trial unblocking of fear learning when Stage II training employed a higher intensity footshock than was used in Stage I (Experiment 2). Systemic administrations of the opioid receptor antagonist naloxone (Experiment 3) or intra-vlPAG administrations of the selective µ-opioid receptor antagonist CTAP (Experiment 4) prior to Stage II training prevented one-trial blocking. These results show that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation.Learning about the predictive relations existing between events in the world is central to adaptive behavior. It allows us to use the past to predict the future and to adjust our behavior accordingly. Prediction has been formalized in experimental psychology through error-correcting learning rules (Dickinson 1980;Rescorla 1988). In Pavlovian conditioning these rules state that fear accrues to a conditioned stimulus (CS) which signals an aversive unconditioned stimulus (US) when the actual outcome of the conditioning trial exceeds the predicted outcome, i.e., when there is a positive prediction error. Likewise, fear to a CS will typically be lost when the predicted outcome exceeds the actual outcome, i.e., when there is a negative prediction error. The paradigmatic demonstration of a role for predictive error in learning is "blocking". Kamin (1968Kamin ( , 1969) subjected rats to CSA-shock pairings. In Stage II, rats received a compound stimulus of CSA and CSB paired with shock. A control group received Stage II training but no Stage I training. The control group showed robust fear of CSB. However, for the experimental group learning to CSB failed. Conditioning failed to CSB, despite AB-shock pairings, because predictive error during Stage II was low: Subjects could predict the occurrence of shock from CSA and so learning about CSB was "blocked."The neural mechanisms for the encoding, storage, and retrieval of fear memories are remarkably well understood. Activation of NMDA receptors in the amygdala and recruitment of the signal transduction cascades subsequent to NMDA receptor activation (e.g., Ca 2+ and cyclic AMP-dependent si...

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“…Local infusion of benzodiazepine agonists into the amygdala produces anxiolytic effects which can be blocked by co-administration of GABA A or benzodiazepine antagonists (Scheel-Kruger and Petersen 1982;Petersen et al 1985; Treit 1994, 1995). Furthermore, the anxietyreducing actions of systemic benzodiazepines can be blocked by intra-amygdala injection of GABA/benzodiazepine antagonists (Sanders and Shekhar 1995).The amygdala also has high levels of endogenous opioid peptides and opioid receptors (Loughlin et al 1995), and opioid mechanisms have been implicated in many biological functions, including nociception, memory, and fear conditioning (Good and Westbrook 1995;McGaugh et al 1996;Valverde et al 1996). A partial anxiolytic action has been reported following microinjection of morphine into amygdala (File and Rodgers 1979).…”

mentioning

confidence: 99%

“…The amygdala also has high levels of endogenous opioid peptides and opioid receptors (Loughlin et al 1995), and opioid mechanisms have been implicated in many biological functions, including nociception, memory, and fear conditioning (Good and Westbrook 1995;McGaugh et al 1996;Valverde et al 1996). A partial anxiolytic action has been reported following microinjection of morphine into amygdala (File and Rodgers 1979).…”

mentioning

confidence: 99%

Overexpression of Proenkephalin in the Amygdala Potentiates the Anxiolytic Effects of Benzodiazepines

Wen

Wilson

2000

Neuropsychopharmacology

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To elucidate the role of opioid peptides in control of the anxiety-like behavior and anxiety-reducing actions of benzodiazepines, a recombinant, replication-defective herpes virus (SHPE) carrying human preproenkephalin cDNA was delivered to rat amygdala. Viral infection resulted in a strong, localized transgene expression after 2-4 days which diminished after one week. Anxiety-like behavior and the anxiolytic effect of diazepam were assessed three days afterIn addition to its well known role in mediating fear and anxiety responses (Davis et al. 1994), the amygdala may also be a key neural substrate for the anxiolytic actions of benzodiazepines. Benzodiazepines (BZs) are believed to induce their anxiolytic properties by binding to GABA/benzodiazepine receptors in the brain (Haefely 1990). In addition, the amygdala has a high density of GABA/benzodiazepine receptors (Young and Kuhar 1980;Richards and Mohler 1984). Local infusion of benzodiazepine agonists into the amygdala produces anxiolytic effects which can be blocked by co-administration of GABA A or benzodiazepine antagonists (Scheel-Kruger and Petersen 1982;Petersen et al. 1985; Treit 1994, 1995). Furthermore, the anxietyreducing actions of systemic benzodiazepines can be blocked by intra-amygdala injection of GABA/benzodiazepine antagonists (Sanders and Shekhar 1995).The amygdala also has high levels of endogenous opioid peptides and opioid receptors (Loughlin et al. 1995), and opioid mechanisms have been implicated in many biological functions, including nociception, memory, and fear conditioning (Good and Westbrook 1995;McGaugh et al. 1996;Valverde et al. 1996). A partial anxiolytic action has been reported following microinjection of morphine into amygdala (File and Rodgers 1979).Although opioid agonists are not used as anxiolytics in general, recent evidence strongly indicates a role for endogenous opioid peptides in the control of stress and anxiety (Olson et al. 1996). Preproenkephalin knockout (Konig et al. 1996), and some novel -opioid agonists show anxiolytic properties (Privette and Terrian 1995). Several lines of evidence also indicate the involvement of endogenous opioid peptides in various aspects of benzodiazepine action, including their influences on food intake, locomotor activity, conflict, and anxiety-like behaviors (Millan and Duka 1981;Cooper 1983;Nowakowska and Chodera 1990). Interestingly, clinical studies suggest interactions between responses to benzodiazepines and opioids in humans (Darke et al. 1993). The anxiolytic effects of benzodiazepines can be blocked by opioid antagonists in both humans and laboratory animals (Billingsley and Kubena 1978;Koob et al. 1980;Duka et al. 1981Duka et al. , 1982Agmo et al 1995;Tsuda et al. 1996).Prior studies using herpes virus-mediated gene transfer demonstrated that overexpression of proenkephalin in amygdala produced antinociceptive effects, and illustrated the usefulness of this methodology for examining the role of neuropeptides in behavioral responses (Kang et al. 1998). To investigate if mo...

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Effects of a microinjection of morphine into the amygdala on the acquisition and expression of conditioned fear and hypoalgesia in rats.

Cited by 91 publications

References 32 publications

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

Opioid receptors mediate direct predictive fear learning: Evidence from one-trial blocking

Overexpression of Proenkephalin in the Amygdala Potentiates the Anxiolytic Effects of Benzodiazepines

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