Abstract
The effects of L-histidine (LH) on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g) using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1) and trial 2 (T2). In T1, mice received an intraperitoneal injection of saline (SAL) or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE) and open-arm time (OAT) (mean +/- SEM; OAE: 4.0 +/- 0.71, 4.80 +/- 1.05; OAT: 40.55 +/- 9.90, 51.55 +/- 12.10, respectively; P > 0.05, Kruskal-Wallis test), or at the dose of 500 mg/kg (OAE: 5.27 +/- 0.73, 4.87 +/- 0.66; OAT: 63.93 +/- 11.72, 63.58 +/- 10.22; P > 0.05, Fisher LSD test). At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT) at the dose of 200 mg/kg (T1: 4.87 +/- 0.66, T2: 5.47 +/- 1.05; T1: 63.58 +/- 10.22; T2: 49.01 +/- 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test) or at the dose of 500 mg/kg (T1: 4.80 +/- 1.60, T2: 4.70 +/- 1.04; T1: 51.55 +/- 12.10, T2: 43.88 +/- 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test), showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.
Highlights
In the mammalian brain, the histaminergic neuron cell bodies are found in the tuberomammillary nucleus of the posterior hypothalamus and these neurons have widespread projections to all major brain areas [1]
The Wilcoxon test showed that the LH-SAL group did not present a reduction of CT in trial 2 (T2) (P = 0.092) and that there was a decrease in %open-arm entries (OAE) for SAL-SAL (P = 0.016) and a decrease in %open-arm time (OAT) for SAL-SAL (P = 0.016) and SAL-LH (P = 0.028)
There is substantial evidence showing that drugs that increase open-arm activity are anxiolytic, while drugs that reduce the open-arm exploration are anxiogenic [33,34]
Summary
The histaminergic neuron cell bodies are found in the tuberomammillary nucleus of the posterior hypothalamus and these neurons have widespread projections to all major brain areas [1]. Studies have indicated the importance of the neural histaminergic system (NHS) in animal behaviors, primarily anxiety [3], learning and memory [4,5]. Some studies describe the inhibitory effects of HA on learning and memory processes [10,11], while others have provided evidence that HA plays a role in reinforcement and mnemonic processes [12,13]. A relationship between the NHS and anxiety has been suggested in studies of the behavior of fish [3,14] and rodents [15,16]. We have reported that chlorpheniramine, a histaminergic H1 receptor antagonist, modulates some components of emotional learning in fish [3]. Kamei and Tasaka [17] showed that the intracerebroventricular (icv) injection of HA and L-histidine (LH) prior to the test caused a significant reduction of the latency response in old rats in an active avoidance response test, facilitating the memory processes. de Almeida and Izquierdo [18] demonstrated that the immediate post-training icv administration of HA facilitated performance in a retention test of step-down inhibitory avoidance behavior measured 24 h later, in rats
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