Simultaneous modulation of retrieval by dopaminergic D-1, beta-noradrenergic, serotonergic-1A and cholinergic muscarinic receptors in cortical structures of the rat

Retrieval of inhibitory avoidance has been recently shown to require intact glutamate receptors, protein kinases A and C and mitogen-activated protein kinase in the CA1 region of the rat hippocampus and in the entorhinal, pos terior parietal and anterior cingulate cortex. These enzymatic activities a re known to be modulated by dopamine D-1, beta -noradrenergic, 5HT1A and ch olinergic muscarinic receptors. Here we study the effect on retrieval of th is task of well-known agonists and antagonists of these receptors infused i n the same brain cortical regions and into the basolateral amygdala, in rat s. The drugs used were SKF38393 (D-1 agonist), noradrenaline, 8-HO-DPAT (5H T1A agonist), oxotremorine (muscarinic agonist), SCH23390 (D-1 antagonist), timolol (beta antagonist), NAN-190 (5HT1A antagonist) and scopolamine (mus carinic antagonist). All were studied at two different dose levels. The loc alised infusion of SKF38393, noradrenaline, NAN-190 and oxotremorine into a ny of the cortical structures mentioned 10 min prior to a 24-h retention te st session of one-trial step-down inhibitory avoidance enhanced retention t est performance. SCH2330, timolol, 8-HO-DPAT and scopolamine hindered reten tion test performance. In the basolateral amygdala only an enhancing effect of noradrenaline and an inhibitory effect of timolol were seen. Three hour s after the infusions, retention test performance returned to normal in all cases. None of the treatments affected locomotion or rearing in an open fi eld or behaviour in the elevated plus maze. Therefore, their effects on ret ention testing can be attributed to an influence on retrieval. In conclusio n, memory retrieval of this apparently simple task requires the participati on of CA1, entorhinal, posterior parietal and anterior cingulate cortex, an d is strongly modulated by, dopaminergic D-1, beta -noradrenergic, muscarin ic cholinergic and 5HT1A receptors in the four areas. The first three types of receptor enhance, and the latter inhibits, retrieval. Only beta -adreno ceptors appears to be involved in the modulation of retrieval of this task by the amygdala. The results bear on the well-known influence of emotion an d mood on retrieval, and indicate that this involves many areas of the brai n simultaneously. In addition, the results point to similarities and differ ences between the modulatory mechanisms that affect retrieval and those inv olved in the consolidation of the same task. (C) 2001 Elsevier Science B.V. All rights reserved.