Abstract: In this study we investigated whether GABA_A receptors of the basolateral amygdala (BLA) interact with the effect of dexamethasone on the retrieval stage of memory. Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery. The animals were trained in step-through apparatus by induction of electric shock (1.5 mA, 3 s) and were tested for memory retrieval after 1 d. The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals’ retrieval in passive avoidance memory. Administration of dexamethasone (0.3 and 0.9 mg/kg, subcutaneously (s.c.)), immediately after training, enhanced memory retrieval. This effect was reduced by intra-BLA microinjection of muscimol (0.125, 0.250 and 0.500 µg/rat), when administered before 0.9 mg/kg of dexamethasone. Microinjection of bicuculline (0.75 µg/rat, intra-BLA) with an ineffective dose of dexamethasone (0.1 mg/kg, s.c.) increased memory retrieval. However, the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes. Our data support reports that dexamethasone enhances memory retrieval. It seems that GABA_A receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.

[1]Baxter, M.G., Murray, E.A., 2002. The amygdala and reward. Nat. Rev. Neurosci., 3(7):563-573.

[2]Bormann, J., 2000. The ‘ABC’ of GABA receptors. Trends Pharmacol. Sci., 21(1):16-19.

[3]Castellano, C., McGaugh, J.L., 1990. Effects of post-training bicuculline and muscimol on retention: lack of state dependency. Behav. Neural Biol., 54(2):156-164.

[4]Cintra, A., Zoli, M., Rosén, L., Agnati, L.F., Okret, S., Wikström, A.C., Gustafsson, J.A., Fuxe, K., 1994. Mapping and computer assisted morphometry and microdensitometry of glucocorticoid receptor immunoreactive neurons in rat central nervous system. Neuroscience, 62(3):843-897.

[5]Dalmaz, C., Introini-Collison, I.B., McGaugh, J.L., 1993. Noradrenergic and cholinergic interactions in the amygdala and the modulation of memory storage. Behav. Brain Res., 58(1-2):167-174.

[6]DiSorbo, A., Wilson, G.N., Bacika, S., Hoxhaa, Z., Biadaa, J.M., Mickleya, G.A., 2009. Time-dependent retrograde amnesic effects of muscimol on conditioned taste aversion extinction. Pharmacol. Biochem. Behav., 92(2):319-326.

[7]Donley, M.P., Schulkin, J., Rosen, J.B., 2005. Glucocorticoid receptor antagonism in the basolateral amygdala and ventral hippocampus interferes with long-term memory of contextual fear. Behav. Brain Res., 164(2):197-205.

[8]Duvarci, S., Paré, D., 2007. Glucocorticoids enhance the excitability of principal basolateral amygdala neurons. J. Neurosci., 27(16):4482-4491.

[9]Emson, P.C., 2007. GABA_B receptors: structure and function. Prog. Brain Res., 160:43-57.

[10]Faber, E.S., Delaney, A.J., Sah, P., 2005. SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala. Nat. Neurosci., 8(5):635-641.

[11]Ferry, B., Roozendaal, B., McGaugh, J.L., 1999. Basolateral amygdale noradrenergic influences on memory storage are mediated by an interaction between β and α₁-adrenoceptors. J. Neurosci., 19(12):5119-5123.

[12]Hatfield, T., Spanis, C., McGaugh, J.L., 1999. Response of amygdalar norepinephrine to footshock and GABAergic drugs using in vivo microdialysis and HPLC. Brain Res., 835(2):340-345.

[13]Izquierdo, I., Cunha, C., Medina, J.H., 1990. Endogenous benzodiazepine modulation of memory processes. Neurosci. Biobehav. Rev., 14(4):419-424.

[14]Khajehpour, L., Rezayof, A., Zarrindast, M.R., 2008. Involvement of dorsal hippocampal nicotinic receptors in the effect of morphine on memory retrieval in passive avoidance task. Eur. J. Pharmacol., 584(2-3):343-351.

[15]Khaksari, M., Rashidy-Pour, A., Vafaei, A.A., 2007. Central mineralocorticoid receptors are indispensable for corticosterone-induced impairment of memory retrieval in rats. Neuroscience, 149(4):729-738.

[16]Macdonald, R.L., Olsen, R.W., 1994. GABA_A receptor channels. Annu. Rev. Neurosci., 17:569-602.

[17]Makara, G.B., Haller, J., 2001. Non-genomic effects of glucocorticoids in the neural system: evidence, mechanisms and implication. Prog. Neurobiol., 65(4):367-390.

[18]Mao, J.B., Robinson, J.K., 1998. Microinjection of GABA-A agonist muscimol into the dorsal but not the ventral hippocampus impairs non-mnemonic measures of delayed non-matching-to-position performance in rats. Brain Res., 784(1-2):139-147.

[19]McGaugh, J.L., 2002. Memory consolidation and the amygdala. Trends Neurosci., 25(9):456-461.

[20]McGaugh, J.L., Roozendaal, B., 2008. Memory Modulation. In: Learning and Memory: A Comprehensive Reference. Elsevier Ltd., Vol. 3, p.521-553.

[21]Michelot, D., Melendez-Howell, L.M., 2003. Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. Mycol. Res., 107(pt2):131-146.

[22]Myhrer, T., 2003. Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res. Rev., 41(2-3):268-287.

[23]Ohno, M., Yamamoto, T., Watanabe, S., 1992. Intrahippocampal injections of benzodiazepine and muscimol impair working memory but not reference memory of rats in the three-panel runway task. Eur. J. Pharmacl., 219(2):245-251.

[24]Olsen, R.W., Sieghart, W., 2009. GABA_A receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology, 56(1):141-148.

[25]Ong, J., Kerr, D.I., 2005. Clinical potential of GABA_B receptor modulators. CNS Drug Rev., 11(3):317-334.

[26]Paré, D., 2003. Role of the basolateral amygdala in memory consolidation. Prog. Neurobiol., 70(5):409-420.

[27]Paxinos, G., Watson, C., 1997. The Rat Brain in Stereotaxic Coordinates, 3 Ed. Academic Press, San Diego, CA, p.15-31.

[28]Power, A.E., Roozendaal, B., McGaugh, J.L., 2000. Glucocorticoid enhancement of memory consolidation in the rat is blocked by muscarinic receptor antagonist in the basolateral amygdala. Eur. J. Neurosci., 12(10):3481-3487.

[29]Quirarte, G.L., Roozendaal, B., McGaugh, J.L., 1997. Glucocorticoid enhancement of memory storage involves noradrenergic activation in the basolateral amygdale. PNAS, 94(25):14048-14053.

[30]Rashidy-Pour, A., Sadeghi, H., Taherain, A.A., Vafaei, A.A., Fathollahi, Y., 2004. The effects of acute restraint stress and dexamethasone on retrieval of long-term memory in rats: an interaction with opiate system. Behav. Brain Res., 154(1):193-198.

[31]Rezayof, A., Khajehpour, L., Zarrindast, M.R., 2009. The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience, 160(2):255-263.

[32]Rodriguez Manzanares, P.A., Isoardi, N.A., Carrer, H.F., Molina, V.A., 2005. Previous stress facilitates fear memory, attenuates GABAergic inhibition, and increases synaptic plasticity in the rat basolateral amygdala. J. Neurosci., 25(38):8725-8734.

[33]Roozendaal, B., McGaugh, J.L., 1996. Amygdaloid nuclei lesions differentially affect glucocorticoid-induced memory enhancement in an inhibitory avoidance task. Neurobiol. Learn. Mem., 65(1):1-8.

[34]Roozendaal, B., McGaugh, J.L., 1997. Glucocorticoid receptor agonist and antagonist administration into the basolateral but not central amygdala modulates memory storage. Neurobiol. Learn. Mem., 67(2):176-179.

[35]Roozendaal, B., Quirarte, G.L., McGaugh, J.L., 2002. Glucocorticoids interact with the basolateral amygdala β-adrenoceptor–cAMP/cAMP/PKA system in influencing memory consolidation. Eur. J. Neurosci., 15(3):553-560.

[36]Roozendaal, B., Hahn, E.L., Nathan, S.V., de Quervain, D.J.F., McGaugh, J.L., 2004. Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala. J. Neurosci., 24(37):8161-8169.

[37]Roozendaal, B., Okuda, S., Quatrain, D.J.F., McGaugh, J.L., 2006. Glucocorticoids interact with emotion-induced noradrenergic activation in influencing different memory functions. Neuroscience, 138(3):901-910.

[38]Roozendaal, B., McEwen, B.S., Chattarji, S., 2009. Stress, memory and the amygdala. Nat. Rev. Neurosci., 10(6):423-433.

[39]Sah, P., Faber, E.S.L., Lopez de Armentia, M., Power, J., 2003. The amygdaloid complex: anatomy and physiology. Physiol. Rev., 83(3):803-834.

[40]Salinas, J.A., McGaugh, J.L., 1996. The amygdala modulates memory for changes in reward magnitude: involvement of the amygdaloid GABAergic system. Behav. Brain Res., 80(1-2):87-98.

[41]Stackman, R.W., Walsh, T.J., 1995. Anatomical specificity and time dependence of chlordiazepoxide-induced spatial memory impairments. Behav. Neurosci., 109(3):436-445.

[42]Stevenson, C.W., Gratton, A., 2003. Basolateral amygdala modulation of the nucleus accumbens dopaminergic response to stress: role of the medial prefrontal cortex. Eur. J. Neurosci., 17(6):1287-1295.

[43]Stevenson, C.W., Sullivan, R.M., Gratton, A., 2003. Effects of basolateral amygdala dopamine depletion on the nucleus accumbens and medial prefrontal cortical dopamine responses to stress. Neuroscience, 116(1):285-293.

[44]Venturella, R., Lessa, D., Luft, T., Roozendaal, B., Schwartsmann, G., Roesler, R., 2005. Dexamethasone reverses the memory impairment induced by antagonism of hippocampal gastrin-releasing peptide receptors. Peptides, 26(5):821-825.

[45]Watanabe, M., Maemura, K., Kanbara, K., Tamayama, T., Hayasaki, H., 2002. GABA and GABA receptors in the central nervous system and other organs. Int. Rev. Cytol., 213:1-47.

[46]Wilensky, A.E., Schafe, G.E., LeDoux, J.E., 2000. The amygdala modulates memory consolidation of fear-motivated inhibitory avoidance learning but not classical fear conditioning. J. Neurosci., 20(18):7059-7066.

[47]Yamada, J., Saitow, F., Satake, S., Kiyohara, T., Konishi, S., 1999. GABA_B receptor-mediated presynaptic inhibition of glutamatergic and GABAergic transmission in the basolateral amygdala. Neuropharmacology, 38(11):1743-1753.

[48]Yamamoto, Y., Mikami, A., Fujii, Y., Kamei, C., 2007. Effect of histamine on muscimol-induced working memory deficits in radial maze performance. J. Pharmacol. Sci., 104(3):252-257.

[49]Zarrindast, M.R., Ahmadi, S., Haeri-Rohani, A., Rezayof, A., Jafari, M.R., Jafari-Sabet, M., 2004. GABA_A receptors in the basolateral amygdala are involved in mediating morphine reward. Brain Res., 1006(1):49-58.