EXPRESS: Pain-dependent learning in healthy volunteers.

A state-dependent learning paradigm was studied in which healthy adult volunteers studied/encoded and recalled information from short passages, neutral in their content, in one of the following conditions: (1) Pain during study-Pain during both recall sessions; (2) Pain during study-No Pain during both recall sessions; (3) No Pain during study-Pain during both recall sessions; and (4) No Pain during study-No Pain during both recall sessions. Pain was experimentally induced using the cold pressor technique. In this study we looked at evidence for state-dependent learning when the context of learning is not emotionally driven, but neutral. The memory task consisted of encoding detailed information about short stories, then recalling as many details as possible 20 minutes and 48 hours later. The results indicated no occurrence of a state-dependent learning and retrieval effect in this sample: participants in the pain-no pain and no pain-pain conditions did not significantly perform differently than participants in the pain-pain and no pain-no pain conditions. However, a main effect of the state during study/encoding was significant, suggesting that being in pain during study had a detrimental effect on performance on the memory tests regardless of the state at retrieval. These results oppose previous studies’ findings and shed new light on possible implications in various research areas.

Cross state-dependency of learning between 5-HT1A and/or 5-HT7 receptor agonists and muscimol in the mouse dorsal hippocampus

Background: Dysfunction of the serotonergic and GABAergic systems in cognitive disorders has been revealed. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help treatment of cognitive disorders. Aims: The aim of the present study was to investigate: 1) 8-OH-DPAT (5-HT1A agonist), AS19 (5-HT7 agonist) and muscimol (GABA-A agonist) on memory retrieval and state of memory, 2) cross state-dependent learning between 8-OH-DPAT and/or AS19 and muscimol. Methods: The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended sites of injection. A single-trial step-down inhibitory avoidance task was used for the evaluation of memory retrieval and state of memory. Results: Post-training and/or pre-test 8-OH-DPAT, AS19 and muscimol induced amnesia. Pre-test microinjection of the same doses of 8-OH-DPAT, AS19 and muscimol reversed the post-training 8-OH-DPAT-, AS19- and muscimol-induced amnesia, respectively. This event has been named state-dependent learning (SDL). The amnesia induced by 8-OH-DPAT was reversed by muscimol and induced 8-OH-DPAT SDL. The amnesia induced by muscimol was reversed by 8-OH-DPAT and induced muscimol SDL. The amnesia induced by AS19 was reversed by muscimol and induced AS19 SDL. The amnesia induced by muscimol was reversed by AS19 and induced muscimol SDL. Pre-test administration of a selective GABA-A receptor antagonist, bicuculline, 5 min before muscimol, 8-OH-DPAT and AS19 dose-dependently inhibited muscimol-, 8-OH-DPAT- and AS19-induced SDL, respectively. Conclusions: The results strongly revealed a cross SDL among 8-OH-DPAT and/or AS19 and muscimol in the dorsal hippocampal CA1 regions.