Effects of α-adrenoceptor agonists and antagonists on histamine-induced impairment of memory retention of passive avoidance learning in rats

doi:10.1016/S0014-2999(02)02497-4

European Journal of Pharmacology

Volume 454, Issues 2–3, 15 November 2002, Pages 193-198

https://doi.org/10.1016/S0014-2999(02)02497-4 Get rights and content

Abstract

The effect of α-adrenoceptor agents on the impairment induced by histamine was measured for memory retention of passive avoidance learning in rats. Post-training intracerebroventricular (i.c.v.) injection was carried out in all the experiments. Histamine (5, 10 and 20 μg/rat) reduced, while a histamine H₁ receptor antagonist, chlorpheniramine (0.1, 1 and 10 μg/rat), increased memory retention. The histamine H₂ receptor antagonist, ranitidine (0.1, 1, 10 and 20 μg/rat), did not elicit any response in this respect. Different doses of chlorpheniramine but not ranitidine reversed the histamine-induced impairment of memory. Clonidine and prazosin decreased, but yohimbine and phenylephrine increased, memory retention. Yohimbine decreased the inhibitory response to histamine. Phenylephrine, clonidine and prazosin did not alter the histamine effect. It is concluded that a histamine-induced impairment of memory retention through histamine H₁ receptors and an α₂-adrenoceptor mechanism may be involved in the histamine response.

Introduction

Accumulating evidence has established histamine as a central neurotransmitter Haas et al., 1991, Schwartz et al., 1991, Ondodera et al., 1994. The tuberomammillary nucleus in the posterior hypothalamus is the major source of neuronal histamine, which projects to numerous brain regions, including neostriatum, hippocampus, and tectum Niigawa et al., 1988, Schwartz et al., 1991. Furthermore, the tuberomammillary nucleus has been implicated in both the processes underlying the functional recovery from brain damage and in the mechanisms of reinforcement, learning, and memory (Huston et al., 1997). However, the functions of the central histaminergic neurons in memory and learning are controversial (Cacabelos and Alvarez, 1991). Histamine functions through three different histamine receptor subtypes; postsynaptic histamine H₁ and H₂ receptors in addition to presynaptic histamine H₃ receptors which control the release of neuronal histamine Prell and Green, 1986, Schwartz et al., 1986, Haas, 1992 and many other neurotransmitters (Schlicker et al., 1994). It was shown that adrenoceptors Hill and Straw, 1988, Gulat-Marnay et al., 1989a and muscarinic receptors (Gulat-Marnay et al., 1989b) influence the release of labeled histamine from decreases histamine release from hypothalamic neurons (Prast and Heistracher, 1991). However, endogenous noradrenaline does not play a physiological role in the release of histamine (Gulat-Marnay et al., 1989a), and no interactions between histamine receptor and α-adrenoceptor systems in learning and memory have not been described. In the present study, depolarized slices of brain cortex. It has also been shown that yohimbine increases and clonidine the possibility of an interaction between the α-adrenoceptor system and histamine H₁ and H₂ receptor agents was investigated.

Section snippets

Animals

Male Wistar rats weighing 200–250 g were used in these experiments. The animals were housed five per cage at room temperature (22–24 °C) with a 12-h light/12-h dark cycle, and food and water ad libitum. Ten animals were used for each experiment.

Cannula guide implantation

The animals were anesthetized with ketamine hydrochloride (50 mg/kg) plus xylazine (rompun; 4 mg/kg). The skull of the rat was fixed to a stereotaxic frame (with David Koft Instruments, USA) and a permanent stainless-steel guide cannula (21 gauge, 0.8

Effect of histamine receptor agonist and antagonists on memory retention in rats

Fig. 1 shows the effects of histamine and histamine receptor antagonists when given intracerebroventricularly (i.c.v.), immediately after the training session. One-way ANOVA indicates a significant difference between results obtained with histamine (5, 10 and 20 μg/rat), the histamine H₁ receptor antagonist, chlorpheniramine (0.1, 1 and 10 μg/rat) and the histamine H₂ receptor antagonist, ranitidine (0.1 1, 10 and 20 μg/rat) [F(11,108)=9.3, P<0.0001]. Further analysis showed that histamine

Discussion

There is evidence that histamine may play a role in learning and memory (Miyazaki et al., 1997) and in modulation of post-training memory processing (Flood et al., 1998).

The present data indicate that post-training administration of different doses of histamine reduced retention latencies. In agreement with the results obtained by other investigators Kamei et al., 1993, Miyazaki et al., 1995, Alvarez and Banzan, 1996, the data may indicate an involvement of the central histaminergic system in

References (34)

M.F. Chen et al.
Noradrenergic mediation of the memory-enhancing effect of corticotropin-releasing factor in the locus coeruleus of rats
Psychoneuroendocrinology
(1992)
C. Frisch et al.
The histamine H₁-antagonist chlorpheniramine facilitates learning in aged rats
Neurosci. Lett.
(1997)
P.E. Gold et al.
The mnemon and its juices: neuromodulation of memory processes
Behav. Neurol. Biol.
(1983)
K. Klapdor et al.
Facilitation of learning in adult and aged rats following bilateral lesions of the tuberomammillary nucleus region
Behav. Brain Res.
(1994)
K.C. Liang et al.
Involvement of amygdala pathway in the influences of post-training intra-amygdala norepinephrine and peripheral epinephrine on memory storage
Brain Res.
(1990)
S. Miyazaki et al.
Effects of thioperamide, a histamine H₃-receptor antagonist, on a scopolamine-induced learning deficit using an elevated plus-maze test in mice
Life Sci.
(1995)
S. Miyazaki et al.
Effects of clobenpropit (VUF-9153), a histamine H₃-receptor antagonist on learning and memory, and on cholinergic and monoaminergic system in mice
Life Sci.
(1997)
H. Niigawa et al.
Effect neurotoxic lesion in the mammillary bodies on the distribution of histamine
Brain Res.
(1988)
D. Quartermain et al.
Attenuation of forgetting by pharmacological stimulation of aminergic neurotransmitter systems
Pharmacol. Biochem. Behav.
(1988)
M. Riekkinen et al.
Effects of combined block of α₁-adrenoceptors and NMDA receptor on spatial and passive avoidance behavior in rats
Eur. J. Pharmacol.
(1996)

J.C. Schwartz et al.

Three classes of histamine receptor in brain

Trends Pharmacol. Sci.

(1986)

E.O. Alvarez et al.

Hippocampal histamine receptors: possible role on the mechanisms of memory in the rat. II

J. Neural Transm.

(1996)

R. Cacabelos et al.

Histidine decarboxylase inhibition induced by u-fluoromethylhistidine provokes learning-related hypokinetic activity

Agents Actions

(1991)

K. Eriksson et al.

Invited Symposium: modulation of activity and function of aminergic neurons in the brain

J.F. Flood et al.

Effect of histamine H₂ and H₃ receptor modulation in the septum on post-training memory processing

Psychopharmacology

(1998)

C. Frisch et al.

Facilitation of learning after lesions of the tuberomammillary nucleus region in adult and aged rats

Exp. Brain Res.

(1998)

C. Gulat-Marnay et al.

Modulation of histamine release and synthesis in the brain mediated by adrenoceptors

J. Neurochem.

(1989)

Cited by (22)

The role of NMDA receptors of the medial septum and dorsal hippocampus on memory acquisition
2016, Pharmacology Biochemistry and Behavior
Citation Excerpt :
The protocols and target coordination of cannula-implantation were according to our previous research (Khakpai et al., 2012a, 2012b). Passive avoidance is one of the most frequently used behavioral paradigms to study neurotransmitter functions involved in learning, long-term memory (Robinson et al., 2011; Zarrindast et al., 2002; Zarrindast et al., 2011), memory consolidation (Izquierdo et al., 2006), diverse forms of cognition (Jafari-Sabet, 2006), and rewarded alternation task (Nagahara and McGaugh, 1992). Passive avoidance task have been many successful inferences to other types of memory, particularly those of fear-motivated learning and spatial tasks.
The glutamatergic neurons in the medial septal/diagonal band of broca (MS/DB) affect the hippocampal functions by modulating the septo-hippocampal neurons. Our study investigated the possible role of NMDA receptors of the medial septum nucleus (MS) and dorsal hippocampus (CA1) on memory acquisition in male Wistar rats. Animals were bilaterally implanted with chronic cannulae in the MS and CA1. Rats were trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency as memory retrieval. Our results indicated that pre-training intra-MS or intra-CA1 infusions of NMDA (0.125 μg/rat) and D-AP7 (0.012 μg/rat) increased and decreased memory acquisition, respectively when compared to saline control group. Also, pre-training intra-CA1 and intra-MS injection of an effect dose of D-AP7 (0.012 μg/rat) along with an effect dose of NMDA (0.125 μg/rat) impaired memory acquisition. Interestingly, pre-training intra-CA1/MS infusion of D-AP7 (0.012 μg/rat) diminished memory response produced by pre-training injection of NMDA (0.125 μg/rat) in the MS/CA1, respectively (cross injection or bilateral injection). Also, all above doses of drugs did not alter locomotor activity. These results suggest that the glutamatergic pathway between the MS and CA1 regions is involved in memory acquisition process.
Hippocampal α-adrenoceptors involve in the effect of histamine on spatial learning
2014, Physiology and Behavior
Spatial learning is a model of higher human cognitive functions which is used for studying animal behavior. Histaminergic and noradrenergic systems play a modulatory role in learning and memory. The present study aimed to test the effects of α-adrenoceptor agonist/antagonist microinjection into the CA1 region of dorsal hippocampus on histamine-induced spatial learning facilitation in the water maze task. Pre-training intra-CA1 microinjection of α₁- or α₂-adrenergic agonist, phenylephrine (0.0025 μg/rat) or clonidine (0.05 μg/rat) decreased traveled distance and escape latency at the start of the training phase, suggesting a spatial learning facilitation; while the higher dose of the drugs (phenylephrine 0.005 μg/rat, clonidine 0.2 and 0.5 μg/rat) increased the performance level at the end of the training phase, indicating a water maze spatial acquisition impairment. However, α₁-receptor antagonist, prazosin (1 μg/rat) impaired spatial learning; α₂-receptor antagonist, yohimbine (0.25 μg/rat) facilitated spatial acquisition. Moreover, pre-training intra-CA1 microinjection of a subthreshold dose of phenylephrine (0.001 μg/rat) reversed histamine response, while ineffective dose co-administration of clonidine (0.1 μg/rat) potentiated histamine (0.01 μg/rat) response. Subthreshold dose of prazosin or yohimbine did not alter histamine response. Bilateral infusion of histamine (0.05 μg/rat) facilitated spatial learning by itself. Furthermore, the drug's injections had no effect on swimming speed on the training days of MWM. These results suggest that α-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in histamine-induced facilitation of spatial acquisition.
The role of the central histaminergic receptors in the exercise-induced improvements of the spatial learning and memory in rats
2014, Brain Research
While it is well known that exercise can improve cognitive performance, the underlying mechanisms are not fully understood. There is now evidence that histamine can modulate learning and memory in different types of behavioral tasks. The present study was designed to examine the possible role of central histamine H₁ and H₂ receptors in forced treadmill running-induced enhancement of learning and memory in rats. For this purpose the animals received intracerebroventricularly chlorpheniramine (H₁ receptor blocker) and cimetidine (H₂ receptor blocker) before each day of fifteen consecutive days of exercise. Then their learning and memory were tested on the water maze task using a four-trial-per-day for 4 consecutive days. A probe trial was performed after the last training day. Our data showed that cimetidine reversed the exercise-induced improvement in learning and memory in rats; however, this was not the case regarding chlorpheniramine. Our findings indicate that central histamine H₂ receptors play an important role in mediating the beneficial effects of forced exercise on learning and memory.
Involvement of the dorsal hippocampal GABA-A receptors in histamine-induced facilitation of memory in the Morris water maze
2013, Pharmacology Biochemistry and Behavior
Citation Excerpt :
It seems that α5GABA-A and NMDA receptors retain a complementary function in hippocampal principal cells' signal transduction control, leading to spatial and temporal memory formation (Mohler et al., 2004). Having three receptor types, histamine mediated pathways are suggested to be involved in learning and memory (Bonini et al., 2011; da Silva et al., 2006; Zarrindast et al., 2002a). In general, H1 (activating phospholipase C and inhibiting potassium channels) and H2 (activating adenylate cyclase) receptors are excitatory, while H3 (inhibiting adenylate cyclase) is typically a presynaptic autoreceptor modulating the release of histamine and other transmitters (Bekkers, 1993; Bianchi et al., 2011).
Several types of learning and memory processes are regulated by the hippocampus which is an important subcortical structure in the mammalians' brain. Previous investigations have shown that different receptor systems in the CA1 region of hippocampus are involved in learning and memory functions. Investigating the possible influence of dorsal hippocampal GABA-A receptors on histamine-induced spatial facilitation in adult male Wistar rats was the focus of the current study. Rats were bilaterally implanted with dorsal hippocampal (CA1) cannulae, recovered from surgery and then trained in Morris water maze (MWM) for 4 consecutive days. A block of four trials was given each day. All drugs were injected into CA1 regions, 5 min before training. Pre-training intra-CA1 microinjection of muscimol, a GABA-A receptor agonist, at the dose of 0.01 or 0.02 μg/rat, increased the traveled distance or the escape latency and traveled distance to the hidden platform, respectively, indicating a water maze spatial acquisition impairment. Intra-CA1 administration of bicuculline, a GABA-A receptor antagonist however, significantly decreased the escape latency and traveled distance to the hidden platform, suggesting a spatial learning facilitation. On the other hand, pre-training intra-CA1 microinjection of the subthreshold dose of muscimol plus different doses of histamine (0.025, 0.05 and 0.1 μg/rat) did not alter the histamine response. Meanwhile, the co-administration of the ineffective dose of bicuculline together with histamine potentiated the spatial learning. Moreover, bilateral infusion of histamine (0.025, 0.05 and 0.1 μg/rat) by itself, facilitated the spatial learning. Notably, the drug injections had no effect on swimming speed during the MWM training sessions. Our results suggest that the dorsal hippocampal (CA1) GABA-A mechanism(s) may influence the histamine-induced facilitation of spatial acquisition.
The histamine H1 receptor and recollection-based discrimination in a temporal order memory task in the mouse
2013, Pharmacology Biochemistry and Behavior
The histaminergic system in the central nervous system is involved in a variety of physiological, pathological and behavioral processes. There is now substantial evidence for an important role of histaminergic neurotransmission in learning and memory related processes. The histamine H1 receptor (H1R) is the most abundant histamine receptor in the mammalian brain. We have recently demonstrated that the genetic inactivation of the H1R in mice impairs episodic-like memory, defined as the ability to remember previous experiences with respect to their content and their temporal and spatial context. The ability to encode and retrieve the temporal order of unique events, that is its temporal context, is a core feature of episodic memory. Here we asked whether episodic-like memory deficits of H1R-KO mice are possibly due to changes in the processing, encoding or maintenance of temporal or sequence information which is critical for episodic-like memory formation. H1R-KO mice were tested in the temporal object memory (TOM) task with different inter-trial intervals (ITIs). H1R-KO mice showed impaired TOM when being tested under both, short and longer ITIs. Another aim of the study was to determine whether temporal order discrimination is based on either familiarity or recollection-based memory processes. The performance of wild type (WT) animals in the TOM task suggests that they used recollection-like discrimination strategies.
Emotional memory consolidation impairment induced by histamine is mediated by H<inf>1</inf> but not H<inf>2</inf> receptors
2012, Brain Research Bulletin
Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have high density in the vermis and flocculus. Evidence indicates that the cerebellar vermis is involved in memory consolidation. Recently, we demonstrated that when histamine is microinjected into the cerebellar vermis it results in impaired emotional memory consolidation in mice that are submitted to the elevated plus maze (EPM). This study investigated whether histamine impairment was mediated by the H₁ or H₂ receptors. The cerebellar vermis of male mice (Swiss Albino) were implanted using a guide cannula. Three days after recovery, behavioral tests were performed in the EPM on two consecutive days (Trial 1 and Trial 2). Immediately after exposure to the EPM (Trial 1), animals received a microinjection of histaminergic drugs. In Experiment 1, saline (SAL) or histamine (HA, 4.07 nmol/0.1 μl) was microinjected 5 min after pretreatment with the H₁ antagonist chlorpheniramine (CPA, 0.16 nmol/0.1 μl) or SAL. In Experiment 2, SAL or HA was microinjected into the mice 5 min after pretreatment with the H₂ antagonist ranitidine (RA, 2.85 nmol/0.1 μl) or SAL. Twenty-four hours later, the mice were re-exposed to the EPM (Trial 2) under the same experimental conditions but did not receive an injection. On both days, the test sessions were recorded to enable analysis of the behavioral measures. The decrease in open arm exploration (% entries and % time spent in the open arms) in Trial 2 relative to Trial 1 was used as a measure of learning and memory. The data were analyzed using the two-way analysis of variance (ANOVA) and Duncan's tests. In Experiment 1, the Duncan's test indicated that the mice entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in Trial 2 after being microinjected with SAL + SAL, SAL + CPA and CPA + HA. However, the animals that received SAL + HA did not enter the open arms less frequently or spend less time in them, which was significantly different from the CPA + HA group. The results of Experiment 2 demonstrated that the %OAE and %OAT in Trial 2 were different from Trial 1 for the groups that were microinjected with SAL + SAL and SAL + RA. The animals that were microinjected with RA + HA or with SAL + HA did not show a reduction in %OAE. These results demonstrate that the animals treated with HA did not avoid the open arms less on retesting and indicated that CPA did not alter the behavior parameters but did revert the histamine-induced impairment of memory consolidation. Furthermore, the H₂ antagonist RA, at the dose used in this study, did not affect memory consolidation and failed to revert histamine-induced impairment.

View all citing articles on Scopus

View full text