Differing time dependencies of object recognition memory impairments produced by nicotinic and muscarinic cholinergic antagonism in perirhinal cortex

Abstract

The roles of muscarinic and nicotinic cholinergic receptors in perirhinal cortex in object recognition memory were compared. Rats' discrimination of a novel object preference test (NOP) test was measured after either systemic or local infusion into the perirhinal cortex of the nicotinic receptor antagonist methyllycaconitine (MLA), which targets alpha-7 (α7) amongst other nicotinic receptors or the muscarinic receptor antagonists scopolamine, AFDX-384, and pirenzepine. Methyllycaconitine administered systemically or intraperirhinally before acquisition impaired recognition memory tested after a 24-h, but not a 20-min delay. In contrast, all three muscarinic antagonists produced a similar, unusual pattern of impairment with amnesia after a 20-min delay, but remembrance after a 24-h delay. Thus, the amnesic effects of nicotinic and muscarinic antagonism were doubly dissociated across the 20-min and 24-h delays. The same pattern of shorter-term but not longer-term memory impairment was found for scopolamine whether the object preference test was carried out in a square arena or a Y-maze and whether rats of the Dark Agouti or Lister-hooded strains were used. Coinfusion of MLA and either scopolamine or AFDX-384 produced an impairment profile matching that for MLA. Hence, the antagonists did not act additively when coadministered. These findings establish an important role in recognition memory for both nicotinic and muscarinic cholinergic receptors in perirhinal cortex, and provide a challenge to simple ideas about the role of cholinergic processes in recognition memory: The effects of muscarinic and nicotinic antagonism are neither independent nor additive.

Contributions of area Te2 to rat recognition memory

“…However, as Te2 is not essential for recognition memory measured after a 20-min delay, this finding cannot exclude an action of AP5 in Te2 on shorter-term recognition memory mechanisms (but if so, these are not essential to task performance). That Te2 is unnecessary for recognition memory measured after a 20-min delay may explain the lack of effect of infusion of the muscarinic receptor antagonist scopolamine; pre-acquisition infusions of scopolamine into PRH impair recognition memory at a 20-min but not a 24-h delay (Warburton et al 2003;Tinsley et al 2011). In contrast, GluK1 kainate receptor antagonism by UBP302 impaired recognition memory after a 24-h delay when infused prior to acquisition into Te2 but left such long-term memory unimpaired when infused into PRH (where it impaired memory after a 20-min delay; Barker et al 2006b).…”

Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function

“…Also, a study by McLean et al showed that, recognition deficits in NOR could be attenuated by PNU-282987, a full agonist of α7-nAChR 23 . According to a study by Tinsley et al 24 , blockade of α7-nAChR by MLA could significantly impair object recognition memory. In a study by Pichat et al, acute treatment with SSR180711 improved recognition memory in object recognition tasks in rats and it was reversed by the α7-nAChR antagonist MLA 14 .…”

Dried bonito broth improves cognitive function via the histaminergic system in mice

“…4). The scopolamine used in the Y-maze model is a muscarinic receptor antagonist, and is also known to cause learning and memory deficits (3,39). The histaminergic neuron system and acetylcholine nervous system are thought to interact and mediate cognitive memory function (2,5,33).…”