Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • The proposed contributory role of

    2021-09-09

    The proposed contributory role of endogenous histamine via activation of H1 receptor in the locomotor sensitization induced by caffeine was further ratified by H1 receptor antagonism during the induction phase and subsequently its effect on expression to locomotor sensitization induced by caffeine. In line with the results of H1 receptor agonist, the i.c.v. administration of H1 receptor antagonist, cetirizine (0.1 μg/mouse) during induction phase with caffeine, significantly attenuated the locomotor sensitization of caffeine (from day 1st to day 13th) (Fig. 2[B]) and also obviated the expression to locomotor sensitization induced by challenging dose of caffeine (10 mg/kg) (Fig. 3[B]) on the expression day (17th day). The locomotor inhibitory effect of H1 receptor antagonist on locomotion is well reported [39,44]. However, we used the locomotor sub-effective dose of the both FMPH and cetirizine to avoid the per se influence of these drugs administration on caffeine induced locomotion in mice. Indeed, FMPH and cetirizine per se in the employed doses failed to alter the basal locomotor activity of mice as compared to aCSF + saline treated group on the first day interaction (Fig. 2[A] and 2 [B] Day 1, respectively). These results comply with report that caffeine potentiates 1-Azakenpaullone mg histaminergic activity to induce wakefulness or reduces sleep via regulation of the H1 receptor [[22], [23], [24]] and the modulatory role of central endogenous histamine on locomotion via H1 receptor stimulation [25]. Therefore, it is construed that enhance endogenous histamine transmission by caffeine administration could contribute to its stimulant effect probably via H1 receptor mediated mechanism. Supporting to this premise, in the brain parenchyma, adenosine deaminase (ADA), an enzyme which catabolizes adenosine to inosine, is dominantly localized in the TMN of the posterior hypothalamus and is colocalized with histamine decarboxylase (HDC) [40], and is the key enzyme for histamine synthesis. Thus, it can be contemplated that caffeine induces its motor stimulant effect via antagonism of adenosine A1 or A2A receptor on histaminergic neurons projecting to VTA and NAc, leading to increase release of histamine in VTA or NAc. This caffeine induced released histamine than could subsequently activate histamine H1 receptor to participate in the action of caffeine induced locomotor sensitization. Supportive to this hypothesis, the dense presence of both adenosine A1 or A2A receptor and histamine H1 receptor is also reported in VTA and NAc [19,41,42]. In contrast to these result, it is also reported that histamine H1 receptors antagonists stimulate the mesolimbic or mesocortical dopamine release and have psychostimulatory behavioral effects [43,44]. Indeed, some histamine H1 receptors antagonists have been reported to increase dopaminergic activity in rats by stimulating the striatal dopaminergic neurons [43]. Thus, in such case, H1 receptors antagonist should have potentiated the effect of caffeine on locomotion rather than the observed attenuation (Fig. 2[A] or [B]). Considering this aberrant nature of results, it can be construed that apart from dopamine, a direct involvement of central histaminergic transmission in the stimulant effect of caffeine cannot be overruled. This speculation is fortified by the reports identifying a dense presence of histamine immunoreactive fibers in VTA and NAc [41] and also that acute caffeine induced locomotor stimulation in attenuated by histamine H1 receptor antagonist [45]. However, there is a dearth of report on the direct affinity of caffeine with histamine H1 receptor. The outcome of the present study adds to the growing body of data delineating the role of central histaminergic transmission in the drug addictive property of caffeine like locomotor stimulation, the main behvioral effect responsible for its abuse. Moreover, the compulsive use pattern of caffeine in the most extreme cases leads to a syndrome termed as “caffeinism” [46]. This condition characterized by a number of behavioral and 1-Azakenpaullone mg physiological symptoms mimicking a primary anxiety disorder. It is noteworthy that central endogenous histamine is also reported by our lab to increase anxiety measure via H1 stimulation [27]. Thus, histamine might also contribute to the caffeine induced anxiety related behvioral effects and more research is warranted in this regard. Therefore, considering the widespread use of caffeine, histamine seems to be a key central target for understanding the neurobiology of caffeine addiction.