Corticosterone enhances long-term retention in one-day-old chicks trained in a weak passive avoidance learning paradigm

Glucocorticoids are released during learning situations and can trigger neural actions through binding to receptors in different brain areas. The possible role of a glucocorticoid action in long-term memory formation was studied, in day-old chicks, by using a passive avoidance task which chicks otherwise only retain for a few hours (< 10) after training. Thus, we examined the effects of intracerebral corticosterone administration on retention 24 h posttraining. The results showed that chicks injected with corticosterone (1 microgram) at either 15 min pretraining or at 5, 30, 60 min (but not 120, 180, or 360 min) posttraining retained the passive avoidance response when tested 24 h posttraining. Studies with specific mineralocorticoid or glucocorticoid receptor antagonists (RU 28318 or RU 38486, respectively) indicated that this increase in retention by corticosterone might be mediated through glucocorticoid receptors. In order to assess whether the facilitatory effect of corticosterone was mediated through an effect on protein synthesis mechanisms, the protein synthesis inhibitor anisomycin was administered prior to corticosterone. However, this treatment only partially attenuated the effect of the steroid, suggesting that corticosterone may influence other cellular processes involved in the formation of long-term memory for the avoidance behaviour.

Piracetam facilitates long-term memory for a passive avoidance task in chicks through a mechanism that requires a brain corticosteroid action

Maria del Carmen Sandi Perez

We investigated the effects of piracetam, a nootropic, on learning and memory formation for a passive avoidance task in day-old chicks. To test for the possible cognitive-enhancing properties of piracetam, a weak learning version of this task--whereby chicks maintain a memory to avoid pecking at a bead coated in a diluted aversant for up to 10 h--was used. Post-training (5, 30 or 60 min), but not pretraining, injections of piracetam (10 or 50 mg/kg, i.p.) increased recall for the task when the chicks were tested 24 h later. Because previous studies showed that long-term memory for the passive avoidance task is dependent upon a brain corticosteroid action, and because the efficacy of piracetam-like compounds is also modulated by corticosteroids, we tested whether the facilitating effect of piracetam was dependent upon a corticosteroid action through specific brain receptors (mineralocorticoid receptor and glucocorticoid receptor). First, increased plasma levels of corticosterone were found 5 min after piracetam injection. In addition, intracerebral administration of antagonists for each receptor type (RU28318, for mineralocorticoid receptors, and RU38486 for glucocorticoid receptors; i.c.) given before the nootropic inhibited the facilitative effect of piracetam on memory consolidation. These results give further support to a modulatory action of piracetam on the mechanisms involved in long-term memory formation through a neural action that, in this learning model, requires the activation of the two types of intracellular corticosteroid receptors.

1998

Effects of NMDA and AMPA receptor antagonists on corticosterone facilitation of long-term memory in the chick

Maria del Carmen Sandi Perez

Long-term memory formation for a weak passive avoidance task in day-old chicks is facilitated by corticosterone administration. Since (i) glutamatergic systems, through different receptor types, play a key role in learning and memory processes, and (ii) glucocorticoids increase glutamate concentrations in learning-related regions of the mammalian brain, we reasoned that glutamatergic activation might be a mechanism by which corticosterone facilitates the formation of an enduring memory. To assess this hypothesis, long-term retention was evaluated in chicks trained on a weak passive avoidance task and intracerebrally injected with NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists (MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione) with regard to training and corticosterone injection respectively. The results indicated that either of the antagonists prevented the facilitating effect of corticosterone when administered before the training trial, but failed to interfere with the steroid effect when injected before corticosterone administration in the post-training period, suggesting that their early effectiveness was not related to corticosterone-induced actions but to training-triggered mechanisms. In addition, administration of the AMPA antagonist, 5.5 h after training, was also effective in impairing the long-term memory-potentiating effect of corticosterone. These results support the view that corticosterone facilitates the formation of an enduring memory in this learning model, through the modulation of late events during the consolidation period, including the activation of the AMPA receptor type.

1997

The corticosteroid synthesis inhibitors metyrapone and aminoglutethimide impair long-term memory for a passive avoidance task in day-old chicks

Maria del Carmen Sandi Perez

Long-term memory for a passive avoidance task in day-old chicks has proved to depend upon an action of the adrenal steroid corticosterone through specific receptors in a brain region, the intermediate medial hyperstriatum ventrale (IMHV), involved in learning the task. In this study, we questioned whether pretraining peripheral administration of drugs described to inhibit either basal levels of corticosterone - aminoglutethimide - or treatment-induced stimulated corticosterone secretion - metyrapone - might interfere with retention for the task at 24 h post-training. The results showed a dose-dependent effect of the inhibitors, with the highest doses tested for both drugs (10 and 50 mg/kg for metyrapone, and 50 mg/kg for aminoglutethimide) being amnestic for the task. Additional experiments, in which we studied possible effects of the inhibitors on concomitant aspects of learning (i.e., reactivity to novelty, and pecking pattern), show that the drugs did not affect general behavioural reactivity. The present results thus support the idea that training-induced corticosterone release plays a key role in the neurobiological processes that determine the establishment of a persistent memory for the aversively motivated avoidance response. In addition, they point to corticosteroid inhibitor drugs as potential tools for the study of the interactions between steroid hormones and cognition-enhancing compounds in this learning task.

1997