The effects of pentylenetetrazol, chlordiazepoxide and caffeine in rats tested in the elevated plus-maze depend on the experimental illumination

García, Andrea; Cárdenas, Fernando P.; Morato, Sílvio

doi:10.1016/j.bbr.2010.09.032

Cited by 37 publications

(20 citation statements)

References 37 publications

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“…Nevertheless, the number of open arm entries were enhanced by caffeine in NVHL rats. But this is usually seen as an expression of enhanced activity rather than anxiolysis (Lister, 1987; Silveira et al, 1993; Bhattacharya et al, 1997; Garcia et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Effects of caffeine or RX821002 in rats with a neonatal ventral hippocampal lesion

Sandner

Angst

Guiberteau

et al. 2014

Front. Behav. Neurosci.

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Rats with a neonatal ventral hippocampal lesion (NVHL) are used to model schizophrenia. They show enhanced locomotion and difficulties in learning after puberty. Such behavioral modifications are strengthened by dopaminergic psychostimulant drugs, which is also relevant for schizophrenia because illustrating its dopaminergic facet. But it remains questionable that only dopaminergic drugs elicit such effects. The behavioral effects could simply represent a non specific arousal, in which case NVHL rats should also be hyper-responsive to other vigilance enhancing drugs. We administered an adenosine (caffeine) or an adrenaline receptor antagonist, (RX821002) at doses documented to modify alertness of rats, respectively 5 mg/kg and 1 mg/kg. Rats were selected prior to the experiments using magnetic resonance imaging (MRI). Each group contained typical and similar NVHL lesions. They were compared to sham lesioned rats. We evaluated locomotion in a new environment and the capacity to remember a visual or acoustic cue that announced the occurrence of food. Both caffeine and RX82100 enhanced locomotion in the novel environment, particularly in NVHL rats. But, RX82100 had a biphasic effect on locomotion, consisting of an initial reduction preceding the enhancement. It was independent of the lesion. Caffeine did not modify the learning performance of NVHL rats. But, RX821002 was found to facilitate learning. Patients tend to intake much more caffeine than healthy people, which has been interpreted as a means to counter some cognitive deficits. This idea was not validated with the present results. But adrenergic drugs could be helpful for attenuating some of their cognitive deficits.

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Section: Discussionmentioning

confidence: 99%

Effects of caffeine or RX821002 in rats with a neonatal ventral hippocampal lesion

Sandner

Angst

Guiberteau

et al. 2014

Front. Behav. Neurosci.

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“…In animal models, caffeine at a moderate dose (30 mg/kg) increases the time rats spend in the open arms of an elevated plus maze (Garcia et al, 2011) indicating that a blockade of adenosine signaling might be anxiolytic. Furthermore, zebra fish with early life anxiety-like behavior can be made less anxious with caffeine (Khor et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Adenosine through the A2A adenosine receptor increases IL-1β in the brain contributing to anxiety

Chiu

Darmody

Walsh

et al. 2014

Brain, Behavior, and Immunity

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Anxiety is one of the most commonly reported psychiatric conditions, but its pathogenesis is poorly understood. Ailments associated with activation of the innate immune system, however, are increasingly linked to anxiety disorders. In adult male mice, we found that adenosine doubled caspase-1 activity in brain by a pathway reliant on ATP-sensitive potassium (KATP) channels, protein kinase A (PKA) and the A2A adenosine receptor (AR). In addition, adenosine-dependent activation of caspase-1 increased interleukin (IL)-1β in the brain by two-fold. Peripheral administration of adenosine in wild-type (WT) mice led to a 2.3-fold increase in caspase-1 activity in the amygdala and to a 33% and 42% reduction in spontaneous locomotor activity and food intake, respectively, that were not observed in caspase-1 knockout (KO), IL-1 receptor type 1 (IL-1R1) KO and A2A AR KO mice or in mice administered a caspase-1 inhibitor centrally. Finally, adenosine administration increased anxiety-like behaviors in WT mice by 28% in the open field test and by 55% in the elevated zero-maze. Caspase-1 KO mice, IL-1R1 KO mice, A2A AR KO mice and WT mice treated with the KATP channel blocker, glyburide, were resistant to adenosine-induced anxiety-like behaviors. Thus, our results indicate that adenosine can act as an anxiogenic by activating caspase-1 and increasing IL-1β in the brain.

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“…In contrast, other studies have reported an anxiolytic response mediated by H 1 receptors in rats and mice (24, 25). The reported discrepancies could be related to experimental differences among the many factors that appear to influence the aversion to open arms, such as the time of day at which testing occurs 26 and the levels of illumination in the testing room (27). …”

Section: Discussionmentioning

confidence: 99%

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

Serafim

Kishi

Canto-de-Souza

et al. 2013

Braz J Med Biol Res

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This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

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The effects of pentylenetetrazol, chlordiazepoxide and caffeine in rats tested in the elevated plus-maze depend on the experimental illumination

Cited by 37 publications

References 37 publications

Effects of caffeine or RX821002 in rats with a neonatal ventral hippocampal lesion

Effects of caffeine or RX821002 in rats with a neonatal ventral hippocampal lesion

Adenosine through the A2A adenosine receptor increases IL-1β in the brain contributing to anxiety

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

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