Introduction It has been recently shown that nitric oxide (NO) and carbon monoxide (CO) in the hippocampus are involved in the early stages of memory processing of an inhibitory avoidance task in rats. 1–5 In addition, electrophysiological evidence suggests that these two highly diffusible gasses act as retrograde intercellular messengers in the induction phase of long-term potentiation (LTP) in the CA1 region of the hippo- campus. 6–9 LTP, a long-lasting activity-dependent form of synaptic plasticity, has been postulated to be involved in certain forms of learning and memory. 5,10–12 NO and CO increase cGMP levels by activating soluble guanylyl cyclases. 13 Quite recently, we were able to demonstrate that the bilateral intrahippocampal injection of 8 Br-cGMP, a membrane-permeable analogue of cGMP, facilitated retention test scores in a step-down inhibitory avoid- ance in rats when given immediately (0 min) but not 180 min after training. 14 Furthermore, a time-depen- dent learning-specific increase in hippocampal cGMP levels was observed immediately post-training. These behavioural and biochemical data strongly suggest that hippocampal cGMP-regulated processes are important in the early stages of memory consolida- tion of an aversively-motivated learning task. In order to determine further the role of hippocampal cGMP signalling pathways in learning and memory, we studied the activity of cGMP- dependent protein kinase (PKG) in the hippocampus of rats trained in an inhibitory avoidance task and the effects of the post-training infusion of LY 83583, an inhibitor of soluble guanylyl cyclase, 15 in memory consolidation of this learning paradigm. Materials and Methods Male Wistar rats (200–240 g) were housed four or five to a cage in a 12:12h light:dark cycle at a temper- ature of 21°C. For cGMP level and PKG activity measurements, the animals were divided into three groups: naive controls, sacrificed by decapitation immediately after withdrawal from their home cage; shocked animals, placed directly over the electrified grid (see below) and receiving a 0.35 mA footshock, and a trained group. Trained rats were placed on a 2.5 cm high, 7  25 cm platform facing a 42  25 cm grid of parallel 0.1 cm stainless steel bars spaced 1 cm apart. Animals received a 0.35 mA, 2 s foot shock immediately they stepped down the platform. At 0, 30 and 180 min after training the rats were sacrificed by decapitation, and the hippocampi were rapidly dissected out on ice. PKG activity was Learning and Memory 1 1 1 1 1 p © Rapid Science Publishers Vol 8 No 9–10 7 July 1997 2221 HIPPOCAMPAL cyclic GMP (cGMP) has been recently postulated to participate in an early phase of memory consolidation of an inhibitory avoidance learning in rats. Here we report on the effects of the intrahippocampal infusion of a soluble guanylyl cyclase inhibitor (LY 83583) in the consolidation of one-trial step-down inhibitory avoidance and on the effect of this task on hippocampal cGMP levels and cGMP-dependent protein kinase (PKG) activity. Bilateral intrahippocampal administration of LY 83583 (2.5 g per side) caused full amnesia for inhibitory avoidance when given immedi- ately (0 min) after training, but not 30 min post-training. Rats submitted to the inhibitory avoidance task showed a significant increase in both cGMP levels and in PKG activity in the hippocampus at 0 min after training. No changes were observed 30 min after training. These find- ings provide further evidence that the hippocampal cGMP/PKG cascade is involved in the early stages of memory formation of an inhibitory avoidance task in rats. Key words: cGMP; Hippocampus; Inhibitory avoidance; Memory; PKG Further evidence for the involvement of a hippocampal cGMP/cGMP-dependent protein kinase cascade in memory consolidation Ramón Bernabeu, Nadja Schroder 1 , Joao Quevedo 1 , Martín Cammarota, Iván Izquierdo 1 and Jorge H. Medina CA Instituto de Biología Celular, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 3 piso, (1121) Buenos Aires, Argentina; 1 Centro de Memoria, Instituto de Biociencias, UFRGS, Porto Alegre, Brazil CA Corresponding Author NeuroReport 8, 2221–2224 (1997)