Glucocorticoid enhancement of memory consolidation in the rat is blocked by muscarinic receptor antagonism in the basolateral amygdala

Abstract

Glucocorticoid-induced memory enhancement is known to depend on beta-adrenoceptor activation in the basolateral amygdala (BLA). Additionally, inactivation of muscarinic cholinergic receptors in the rat amygdala blocks memory enhancement induced by concurrent beta-adrenergic activation. Together, these findings suggest that glucocorticoid-induced modulation of memory consolidation requires cholinergic as well as adrenergic activation in the BLA. Two experiments investigated this issue. The first experiment examined whether blockade of muscarinic cholinergic receptors in the BLA with atropine alters the memory-enhancing effects of the systemically administered glucocorticoid dexamethasone. Dexamethasone (0.3, 1.0 or 3.0 mg/kg, s.c.) administered to rats immediately after inhibitory avoidance training produced dose-dependent enhancement of 48-h retention. Concurrent bilateral infusions of the muscarinic cholinergic antagonist atropine (0.5 microg in 0.2 microL per side) into the BLA blocked the memory enhancement. The second experiment investigated whether the BLA is a locus of interaction between glucocorticoid and muscarinic activation. The specific glucocorticoid receptor (GR or type II) agonist RU 28362 (1.0, 3.0 or 10 ng) was infused into the BLA either alone or together with atropine immediately after training. The GR agonist produced dose-dependent memory enhancement and atropine blocked the memory enhancement. These findings indicate that muscarinic cholinergic activation within the BLA is critical for enabling glucocorticoid enhancement of memory consolidation and that enhancement of memory induced by GR activation in the BLA requires cholinergic activation within the BLA.

Memory enhancement induced by post-training intrabasolateral amygdala infusions of β-adrenergic or muscarinic agonists requires activation of dopamine receptors: Involvement of right, but not left, basolateral amygdala

“…Previous studies indicate that the memorymodulating effects of drugs affecting the opioid-peptidergic or glucocorticoid systems require ␤-adrenoceptor activation in the BLA and that the memory-modulating effects of drugs affecting the glucocorticoid or noradrenergic systems require muscarinic receptor activation in the BLA (McGaugh et al 1988;IntroiniCollison et al 1996;Quirarte et al 1997;Power et al 2000). Such findings suggested that there is a sequential "order" of effects of these systems, and the muscarinic receptors appeared to be the most "downstream" system in the BLA in influencing memory consolidation.…”

“…Post-training intra-BLA infusions of ␤-adrenoceptor antagonists block the memory-enhancing effects of opioid-peptidergic antagonists, glucocorticoid agonists, and DA (McGaugh et al 1988;Quirarte et al 1997;LaLumiere et al 2004). Similarly, post-training intra-BLA infusions of muscarinic cholinergic antagonists block the memory-enhancing effects of glucocorticoid agonists, ␤-adrenergic agonists, and DA (Introini-Collison et al 1996;Power et al 2000;LaLumiere et al 2004).Studies of the effects of DA receptor antagonists provide additional evidence suggesting that the dopaminergic system in the BLA is also critically involved in memory modulation. Post-training intra-BLA infusions of a D1 or D2 receptor antagonist impair retention for inhibitory avoidance (IA) training (LaLumiere et al 2004), and post-training intra-BLA infusions of the nonspecific DA receptor antagonist cis-Flupenthixol (Flu) block the memory enhancement induced by intranucleus accumbens shell infusions of DA (LaLumiere et al 2005).…”

“…Post-training intra-BLA infusions of ␤-adrenoceptor antagonists block the memory-enhancing effects of opioid-peptidergic antagonists, glucocorticoid agonists, and DA (McGaugh et al 1988;Quirarte et al 1997;LaLumiere et al 2004). Similarly, post-training intra-BLA infusions of muscarinic cholinergic antagonists block the memory-enhancing effects of glucocorticoid agonists, ␤-adrenergic agonists, and DA (Introini-Collison et al 1996;Power et al 2000;LaLumiere et al 2004).…”

Involvement of basolateral amygdala GABAA receptors in the effect of dexamethasone on memory in rats

“…The activation of glucocorticoid-sensitive pathways by the administration of agonists of these hormones after training, enhances memory consolidation (Power et al, 2000;Paré, 2003;Roozendaal et al, 2006). Glucocorticoids act via intracellular receptors (genomic pathway) and membrane receptors (Makara and Haller, 2001).…”

“…The basolateral nuclei of the amygdala mediate the effects of some hormones and neurotransmitters on memory formation (Power et al, 2000;McGaugh and Roozendaal, 2008) and connect the amygdala to other regions of the brain, such as the hippocampus and the prefrontal cortex, that are involved in the processes of memory (Roozendaal et al, 2009).…”