Impaired Memory Consolidation in Rats Produced with β-Adrenergic Blockade

doi:10.1006/nlme.1999.3950

Neurobiology of Learning and Memory

Volume 74, Issue 3, November 2000, Pages 259-266

https://doi.org/10.1006/nlme.1999.3950 Get rights and content

Abstract

Despite abundant evidence that systemic administration of adrenergic drugs and hormones can produce retrograde memory enhancement, the literature contains no clear demonstration that postlearning systemic administration of adrenergic antagonists produces retrograde amnesia. Here we demonstrate retrograde amnesia for a stressful learning task (a spatial water maze) with systemic administration of the β-adrenergic antagonist propranolol (5 mg/kg). The amnesic effect of the drug depended on the degree of learning in the subjects: Propranolol caused a robust retrograde amnesia in “good learners,” but did not significantly affect memory in “poor learners.” The findings provide critical additional support for the hypothesis that postlearning adrenergic activation modulates memory consolidation processes after emotionally stressful events and help explain previous failures to detect memory impairment after systemic administration of adrenergic blocking drugs.

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Somatic and motivational symptoms accompanying opiate withdrawal are considered one of the major reasons for relapse to opiate-seeking and opiate-taking behaviors. These symptoms are accompanied by the activation of stress-related processes including hypothalamic-pituitary-adrenal axis activity and noradrenergic (NA) signaling. In particular, the NA system plays an important role in the expression of somatic signs of opiate withdrawal, whereas glucocorticoid (GR) and mineralocorticoid receptors (MR) are activated during opiate abstinence.
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Together, our results demonstrate the important roles of noradrenergic receptors in the modulation of somatic, but not motivational/affective, symptoms of morphine withdrawal. In addition MR but not GR regulates the expression of only somatic symptoms of morphine withdrawal.
Voluntary exercise or systemic propranolol ameliorates stress-related maladaptive behaviors in female rats
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Many people will experience at least one traumatic event in their lifetime, with up to 20% developing Post-Traumatic Stress Disorder (PTSD) or PTSD-like symptoms. In addition, the likelihood that females will develop PTSD after trauma is more than twice that of males. Despite its prevalence, current treatment strategies for trauma victims are limited and substantial portions of affected individuals remain resistant to treatment, suggesting that additional interventions are necessary. Using an animal model of traumatic stress, the present studies tested the hypothesis that either voluntary exercise and/or administration of the adrenergic beta-receptor antagonist propranolol, would ameliorate stress-related maladaptive behaviors. In Study 1 four groups of female rats were exposed to a sequence of stressors that included anesthesia, restraint, forced swim, exposure to predator scent and fear conditioning. Rats then underwent re-exposure sessions in which stress-related conditioned stimuli were presented. In addition to re-exposure, stressed rats were treated with propranolol (10 mg/kg) and/or given the opportunity to engage in voluntary wheel running intermittently for 4 weeks. Stress-associated maladaptive behavior was assessed using the elevated plus and open field mazes and fear memory tests. Cognitive ability was assessed using a novel odor recognition task. A main effect of exercise on behaviors related to anxiety and resilience was observed, but neither a main effect of propranolol nor a synergistic effect of propranolol and exercise were observed. Neither stress induction nor treatment influenced recognition memory. In contrast, in Study 2 in which the timing and dosage of propranolol (0.25–2.0 mg/kg), and the number and timing of re-exposure sessions were adjusted, propranolol produced both a reduction in anxiety-like behaviors as well as resilience to a subsequent stressor. These results are consistent with the notion that combining re-exposure therapy with additional interventions is beneficial for female trauma victims. Furthermore, the findings support the view that in pre-clinical models, voluntary exercise, which bolsters hippocampal function and propranolol, which affects amygdala-dependent memory reconsolidation and peripheral noradrenergic signaling, can ameliorate stress-related symptoms.
Propranolol disrupts consolidation of emotional memory in Lymnaea
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The therapeutic efficacy of the synthetic β-adrenergic receptor blocker, propranolol, for the treatment of post-traumatic stress disorder (PTSD) is currently being debated. Mixed results have been published regarding propranolol’s ability to disrupt the consolidation and reconsolidation of memories. Here, we use the invertebrate model Lymnaea to study propranolol’s ability to disrupt consolidation of memories formed under varying various types of stress which cause differing degrees of emotional memory. We show that when propranolol is administered immediately following operant conditioning, only the consolidation process of memories enhanced by individual stressors (i.e. a non-emotional memory) is susceptible to disruption. However, when propranolol is administered prior to training, only memories enhanced by a combination of stressors leading to an emotional memory are susceptible to disruption. These data suggest that the time of propranolol administration, as well as the type of memory formed play a key role in propranolol’s ability to obstruct memory consolidation.
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Environmental rewards and Pavlovian reward cues can acquire incentive salience, thereby eliciting incentive motivational states and instigate reward-seeking. In rats, the incentive salience of food cues can be measured during a Pavlovian conditioned approach paradigm, in which rats engage in cue-directed approach (“sign-tracking”) or approach the food delivery location (“goal-tracking”). While it has been shown that dopamine signaling is necessary for sign-tracking, some studies have suggested that norepinephrine is involved in learning to sign-track as well. Thus, in order to investigate the influence of norepinephrine in Pavlovian conditioned approach, we administered three adrenergic drugs while rats learned that a food cue (an illuminated, retractable lever) preceded the delivery of banana-flavored food pellets into a food-cup. We found that pre-session injections of disulfiram (a dopamine-β-hydroxylase inhibitor) inhibited the development of sign-tracking, but goal-tracking was only affected at the high dose. In one experiment, post-session injections of disulfiram blocked the development of sign-tracking, although this effect was not replicated in a separate set of rats. Post-session injections of prazosin (an α1-adrenergic receptor antagonist) and propranolol (a β-adrenergic receptor antagonist) also blocked the development of sign-tracking but not goal-tracking. Taken together, these results suggest that adrenergic transmission mediates the acquisition of sign-tracking but not goal-tracking, and thus plays a selective role in the attribution of incentive salience food cues.
The Effects of β-Adrenergic Blockade on the Degrading Effects of Eye Movements on Negative Autobiographical Memories
2017, Biological Psychiatry
Citation Excerpt :
These effects were found at the posttest (immediately after the EM intervention) and at the follow-up (24 hours later). Since propranolol is known to impair memories by interfering with (re)consolidation (37–39), the present effects can be accounted for by attenuation of noradrenergic neurotransmission induced by propranolol, thereby blocking superior reconsolidation of the degraded memory. Alternatively, the observed effects might be explained by WM taxation.
Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During EMDR, patients make horizontal eye movements (EMs) while simultaneously recalling a traumatic memory, which renders the memory less vivid and emotional when it is later recalled again. Recalling highly emotional autobiographical memories enhances noradrenergic neurotransmission. Noradrenaline (NA) strengthens memory (re)consolidation. However, memories become less vivid after recall+EMs. Therefore, NA might either play no significant role or serve to strengthen memories that are degraded by EMs. The present study was designed to test the latter hypothesis. We predicted that blocking NA would abolish the memory degrading effects of EMs.
Fifty-six healthy participants selected three negative autobiographical memories. One was then recalled while making EMs, one was recalled without EMs, and one was not recalled. Vividness and emotionality of the memories as well as heart rate and skin conductance level during memory retrieval were measured before, directly after, and 24 hours after the EM task. Before the task, participants received a placebo or the noradrenergic β-receptor blocker propranolol (40 mg).
There were no effects of EMs on memory emotionality or psychophysiological measures in the propranolol and placebo groups. However, in the placebo group, but not in the propranolol group, memory vividness significantly decreased from pretest to posttest and follow-up after recall+EMs relative to the control conditions.
Blocking NA abolished the effects of EMs on the vividness of emotional memories, indicating that NA is crucial for EMDR effectiveness and possibly strengthens the reconsolidation of the degraded memory.

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^f1: Address correspondence and reprint requests to Larry Cahill, CNLM, UC Irvine, California 92697-3800. Fax: (949) 824-5244. E-mail: [email protected].

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Regular ArticleImpaired Memory Consolidation in Rats Produced with β-Adrenergic Blockade

Abstract

Progress in Brain Research

Pharmacology Biochemistry and Behavior

Trends in Neuroscience

Pharmacology Biochemistry and Behavior

Brain Research

Behavioral Brain Research

Behavioral and Neural Biology

Neurobiology of Learning and Memory

Behavioral Brain Research

Pharmacology Biochemistry and Behavior

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Facilitation of maze learning with posttrial injections of picrotoxin

Journal of Comparative and Physiological Psychology

β-Adrenergic activation and memory for emotional events

Nature

Memory formation: Evidence for a specific neurochemical system in the amygdala

Science

Regular Article
Impaired Memory Consolidation in Rats Produced with β-Adrenergic Blockade