Participation of Hippocampal 5-HT5A, 5-HT6 and 5-HT7 Serotonin Receptors on the Consolidation of Social Recognition Memory.

Social recognition is the ability of animals to identify and recognize a conspecific. The consolidation of social stimuli in long-term memory is crucial for the establishment and maintenance of social groups, reproduction and species survival. Despite its importance, little is known about the circuitry and molecular mechanisms involved in the social recognition memory (SRM). Serotonin (5-hydroxytryptamine, 5-HT) is acknowledged as a major neuromodulator, which plays a key role in learning and memory. Focusing on the more recently described 5-HT receptors, we investigated in the CA1 region of the dorsal hippocampus the participation of 5-HT5A, 5-HT6 and 5-HT7 receptors in the consolidation of SRM. Male Wistar rats cannulated in CA1 were subjected to a social discrimination task. In the sample phase the animals were exposed to a juvenile conspecific for 1 h. Immediately after, they received different pharmacological treatments. Twenty-four hours later, they were submitted to a 5 min retention test in the presence of the previously presented juvenile (familiar) and a novel juvenile. The animals that received infusions of 5-HT5A receptor antagonist SB-699551 (10 µg/µL), 5-HT6 receptor agonist WAY-208466 (0.63 µg/µL) or 5-HT7 receptor agonist AS-19 (5 µg/µL) intra-CA1 were unable to recognize the familiar juvenile. This effect was blocked by the coinfusion of WAY-208466 plus 5-HT6 receptor antagonist SB-271046 (10 µg/µL) or AS-19 plus 5-HT7 receptor antagonist SB-269970 (5 µg/µL). The present study helps to clarify the neurobiological functions of the 5-HT receptors more recently described and extends our knowledge about mechanisms underlying the SRM.

Methylphenidate induces state-dependency of social recognition learning: Central components.

Methylphenidate (MPH) is a widely prescribed drug for the treatment of attention-deficit hyperactivity disorder. Findings in the literature suggest that the effects of MPH on memory may result from increased extracellular levels of norepinephrine (NE) and dopamine (DA). Here, we report that the systemic administration of MPH before the acquisition phase in a social discrimination task impaired the retrieval of the social recognition memory (SRM), but made it state-dependent: another administration of MPH before the retention test recovered the SRM. We observed that the induction of state dependency by MPH relies on the ventromedial prefrontal cortex (vmPFC), but not on the CA1 region of the hippocampus (CA1). Also, the inhibitors of NE and DA, nisoxetine and GBR12909, respectively, restored the SRM when infused into the vmPFC. Only the GBR12909 was able to restore the SRM in the CA1, whereas nisoxetine could not restore and even caused an impairment on memory retrieval when infused alone before the retention test. The data suggest that the state-dependence of SRM induced by MPH depends on an influence of both catecholamines on the vmPFC, while NE inhibits the retrieval of SRM on the hippocampus.

Major neurotransmitter systems in dorsal hippocampus and basolateral amygdala control social recognition memory.

Social recognition memory (SRM) is crucial for reproduction, forming social groups, and species survival. Despite its importance, SRM is still relatively little studied. Here we examine the participation of the CA1 region of the dorsal hippocampus (CA1) and the basolateral amygdala (BLA) and that of dopaminergic, noradrenergic, and histaminergic systems in both structures in the consolidation of SRM. Male Wistar rats received intra-CA1 or intra-BLA infusions of different drugs immediately after the sample phase of a social discrimination task and 24-h later were subjected to a 5-min retention test. Animals treated with the protein synthesis inhibitor, anisomycin, into either the CA1 or BLA were unable to recognize the previously exposed juvenile (familiar) during the retention test. When infused into the CA1, the ß-adrenoreceptor agonist, isoproterenol, the D1/D5 dopaminergic receptor antagonist, SCH23390, and the H2 histaminergic receptor antagonist, ranitidine, also hindered the recognition of the familiar juvenile 24-h later. The latter drug effects were more intense in the CA1 than in the BLA. When infused into the BLA, the ß-adrenoreceptor antagonist, timolol, the D1/D5 dopamine receptor agonist, SKF38393, and the H2 histaminergic receptor agonist, ranitidine, also hindered recognition of the familiar juvenile 24-h later. In all cases, the impairment to recognize the familiar juvenile was abolished by the coinfusion of agonist plus antagonist. Clearly, both the CA1 and BLA, probably in that order, play major roles in the consolidation of SRM, but these roles are different in each structure vis-à-vis the involvement of the ß-noradrenergic, D1/D5-dopaminergic, and H2-histaminergic receptors therein.