LAUSR

Garnered literature points towards the role of the dorsal hippocampus (CA1) in ethanol withdrawal-induced responses, wherein a strong presence of the histaminergic system is also reported. Therefore, the present study investigated the effect of an enhanced CA1 histaminergic transmission on the expression of chronic ethanol withdrawal-induced despair in mice on tail suspension test (TST). The results revealed that mice who were on an ethanol-fed diet (5.96%, v/v) for 8 days, exhibited maximum immobility time on TST, and decreased locomotion at 24 h post ethanol withdrawal (10th day), indicating ethanol withdrawal-induced despair. Enhancement of CA1 histaminergic activity achieved by the treatment of intra-CA1 microinjection of histaminergic agents like histamine (0.1, 10 μg/mouse, bilateral), histamine precursor, L-histidine (1, 10 μg/mouse, bilateral), histamine neuronal releaser/H3 receptor antagonist, thioperamide (2, 10 μg/mouse, bilateral), histamine H1 receptor agonist, FMPH (2, 6.5 μg/mouse, bilateral), or H2 receptor agonist amthamine (0.1, 0.5 μg/mouse, bilateral) to ethanol withdrawn mice, 10 min before 24 h post-ethanol withdrawal time point significantly alleviated the expression of ethanol withdrawal-induced despair in mice on TST. On the other hand, only the pre-treatment of histamine H1 receptor agonist, FMPH (2, 6.5 μg/mouse, intra-CA1 bilateral) reversed the reduction in locomotor activity induced in ethanol withdrawn mice, wherein other employed histaminergic agents were devoid of any effect on this behavior. Therefore, our findings indicate that an enhanced CA1 histaminergic transmission probably via stimulation of CA1 postsynaptic histamine H1 or H2 receptor could preclude the behavioral despair, whilst H1 stimulation affects motor deficit expressed after ethanol withdrawal.