Research reportIndispensable role of the voltage-gated calcium channels in the procognitive effects of angiotensin IV

•Angiotensin IV (Ang IV) given intracerebroventriculary improves memory in rats.•Nimodipine and Mibefradil given orally before Ang IV abolish this effect.•L- and T-type calcium channels are involved in memory enhancing effects of Ang IV.

BackgroundVoltage-gated calcium channels (VGCCs) play a major role in brain functioning, including that of cognition-related structures such as cerebral cortex and hippocampus. Cellular mechanisms underlying learning and memory enhancing effect of the neuropeptide angiotensin IV (Ang IV) have been linked to VGCCs but only in respect of its long-term potentiation (LTP)-inducing effect.ObjectiveTo assess behaviorally effects of L- and T-type VGCCs blocking drugs in low, behaviorally inactive, doses on Ang IV facilitation of recall of aversively (foot-shock) and appetitively (curiosity for novelty) motivated behaviors.MethodsAbout 240 male Wistar rats were used. All animals received oral (p.o.) dose of nimodipine (12 mg/kg) or mibefradil (1 mg/kg) dissolved in saline or saline alone followed by an intracerebroventricular (i.c.v.) injection of 1 nmol of Ang IV dissolved in 2 μl of normal saline or saline alone 15 min later. Groups of about 10 rats, separate for each experiment, were tested for recall of aversively (inhibitory avoidance, IA) and appetitively (object recognition, OR) reinforced behaviors. To verify lack of unspecific motor and emotional effects of our treatments separate groups of rats were tested in open field (OF) and elevated 'plus' maze (EPM), respectively.ResultsBoth, nimodipine and mibefradil prevented recall facilitating effects of subsequently injected Ang IV. The peptide as well as both VGCCs blocking drugs had no (OF), or only negligible (EPM) effects on motor performance and emotionality of rats.ConclusionThe data support a notion about key role of the functional VGCCs in neuronal procognitive effects of Ang IV.

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