Serotonergic Systems In Modulation Research Articles

Interactions between the cannabinoid and the serotonergic systems in modulation of pain perception

The aim of our study was to evaluate the effects of cannabinoids and serotonergic system on nociception in intact rats and after heat stress. Cannabinoid receptor type 1 (CB1) and 5-hydroxytryptamine receptor (5НТ1А) agonists and antagonists have been administered according to different experimental designs (alone and in combinations) in intact male Wistar rats, as well in animals subjected to one hour of heat stress. Pain perception has been evaluated by Paw pressure test. Our results pointed out that cannabinoids and the serotonergic system interact in nociception in intact animals as well as after heat stress. Cannabinoids seemed to have less prominent role in such interaction in intact animals than after heat stress. The interplay between the two systems probably involves different mechanisms in intact animals and after heat stress with time-dependent effects. The interaction between the cannabinoid and the serotonergic systems exerts a modulating rather than mediating effect on h-SIA.

Interaction between harmane, a class of β-carboline alkaloids, and the CA1 serotonergic system in modulation of memory acquisition

This study set to assess the involvement of dorsal hippocampus (CA1) serotonergic system on harmane induced memory acquisition deficit. We used one trial step-down inhibitory avoidancetask to evaluate memory retention and then, open field test to evaluate locomotor activity in adult male NMRI mice. The results showed that pre-training intra-peritoneal (i.p.) administration of harmane (12mg/kg) induced impairment of memory acquisition. Pre-training intra-CA1 administration of 5-HT1B/1D receptor agonist (CP94253; 0.5 and 5ng/mouse) and 5-HT2A/2B/2C receptor agonist (α-methyl 5-HT; 50ng/mouse) impaired memory acquisition. Furthermore, intra-CA1 administration of 5-HT1B/1D receptor antagonist (GR127935; 0.5ng/mouse) and 5-HT2 receptor antagonist (cinancerine; 5ng/mouse) improved memory acquisition. In addition, pre-training intra-CA1 injection of sub-threshold dose of CP94253 (0.05ng/mouse) and α-methyl 5-HT (5ng/mouse) potentiated impairment of memory acquisition induced by harmane (12mg/kg, i.p.). On the other hand, pre-training intra-CA1 infusion of sub-threshold dose of GR127935 (0.05ng/mouse) and cinancerine (0.5ng/mouse) with the administration of harmane (12mg/kg, i.p.) weakened impairment of memory acquisition. Moreover, all above doses of drugs did not change locomotor activity. The present findings suggest that there is an interaction between harmane and the CA1 serotonergic system in modulation of memory acquisition.

Oxidative stress and age-related olfactory memory impairment in the honeybee Apis mellifera.

is one of the most impor-tant insect species to study olfactorylearning and memory because it canbe conditioned to respond with feed-ing movements of the mouthparts (pro-boscis)to avariety offloral odors by usingProboscis Extension Reflex (PER) condi-tioning. Honeybee workers switch fromin-hive (nursing) to outside-hive (forag-ing) tasks depending on their age, colonydemand, and outside conditions. Workersuse their sophisticated cognitive abilitiesin both foraging, and task performancewithin the colony (Menzel and Giurfa,2001; Frasnelli et al., 2014). The honey-bee olfactory system possesses olfactorysensory neurons inside the cuticle-coveredsensillae along the antennae, which areequivalenttoolfactoryepitheliawithinthenasal cavity in vertebrates. From antennathe information is carried via axons ofolfactory sensory neurons directly to theantennal lobe (AL) that is equivalent tothe olfactory bulb (OB) in vertebrates.This information is processed in the ALthen relayed by projection neurons tothe mushroom bodies (MB), which con-tribute to memory consolidation asso-ciated with long-term potentiation andsynaptic organization (Hourcade et al.,2010).Theexhibitingsynapticplasticityinthe MB is similar to that of mammalianhippocampal synaptic plasticity (Bliss andCollingridge, 1993).The neuronal synaptic plasticity canbe regulated by important signalingmolecules called as “biogenic amines”that modulate synaptic morphology,number of synapses, and receptors,influencing animal behaviors includ-ing complex behaviors such as learningand memory formation in both ver-tebrates and invertebrates. Prominentexamples of biogenic amines includeepinephrine, norepinephrine, dopamine,serotonin, octopamine, and tyramine.Norepinephrine and epinephrine arepreferentially synthesized by vertebrates;whereas octopamine and tyramine arepreferentially synthesized by invertebrates.Biogenic amines exert their activity byinteracting with specific G-protein cou-pled receptors, causing changes in thelevels of intracellular second messengers(Scheiner et al., 2006). In vertebrates,both the OB and cortex receive heavyinputs from cholinergic, noradrenergic,and serotonergic modulatory systems,exerting profound effects on both odorprocessing and odor memory by actingon both inhibitory local interneurons γ-amino butyric acid (GABA) and outputneurons in both regions (Fletcher andChen, 2010). The primary sensory affer-ents from the olfactory neuroepitheliumto OB can be modulated by a presynap-tic inhibition-mediated by GABA anddopamine released from bulbar interneu-rons. Increased levels of octopamine inthe AL mediate an important role in areinforcementpathwayinvolvingolfactorylearning and memory in

Neural correlates of olfactory learning: Critical role of centrifugal neuromodulation

The mammalian olfactory system is well established for its remarkable capability of undergoing experience-dependent plasticity. Although this process involves changes at multiple stages throughout the central olfactory pathway, even the early stages of processing, such as the olfactory bulb and piriform cortex, can display a high degree of plasticity. As in other sensory systems, this plasticity can be controlled by centrifugal inputs from brain regions known to be involved in attention and learning processes. Specifically, both the bulb and cortex receive heavy inputs from cholinergic, noradrenergic, and serotonergic modulatory systems. These neuromodulators are shown to have profound effects on both odor processing and odor memory by acting on both inhibitory local interneurons and output neurons in both regions.

Drugs of Abuse Specifically Sensitize Noradrenergic and Serotonergic Neurons Via a Non-Dopaminergic Mechanism

A challenge in drug dependence is to delineate long-term neurochemical modifications induced by drugs of abuse. Repeated d-amphetamine was recently shown to disrupt a mutual regulatory link between noradrenergic and serotonergic neurons, thus inducing long-term increased responses to d-amphetamine and para-chloroamphetamine, respectively. We show here that such a sensitization of noradrenergic and serotonergic neurons also occurs following repeated treatment with cocaine, morphine, or alcohol, three compounds belonging to main groups of addictive substances. In all cases, this sensitization is prevented by alpha 1b-adrenergic and 5-HT2A receptors blockade, indicating the critical role of these receptors on long-term effects of drugs of abuse. However, repeated treatments with two non-addictive antidepressants, venlafaxine, and clorimipramine, which nevertheless inhibit noradrenergic and serotonergic reuptake, do not induce noradrenergic and serotonergic neurons sensitization. Similarly, this sensitization does not occur following repeated treatments with a specific inhibitor of dopamine (DA) reuptake, GBR12783. Moreover, we show that the effects of SCH23390, a D1 receptor antagonist known to inhibit development of d-amphetamine behavioral sensitization, are due to its 5-HT2C receptor agonist property. SCH23390 blocks amphetamine-induced release of norepinephrine and RS102221, a 5-HT2C antagonist, can reverse this inhibition as well as inhibition of noradrenergic sensitization and development of behavioral sensitization induced by repeated d-amphetamine. We propose that noradrenergic/serotonergic uncoupling is a common neurochemical consequence of repeated consumption of drugs of abuse, unrelated with DA release. Our data also suggest that compounds able to restore the link between noradrenergic and serotonergic modulatory systems could represent important therapeutic targets for investigation.

Serotonin-mediated increases in the extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens: a microdialysis study.

Although the involvement of both endogenous opioid and serotonergic systems in modulation of pain and emotion was suggested, the neurochemical interaction between these systems in the brain has not previously been studied directly. Herein, the effects of the local application of serotonin (5-HT) and fluoxetine (a 5-HT reuptake inhibitor) on extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens were assessed in freely moving rats using in vivo microdialysis. The mean basal concentrations of beta-endorphin in dialysates obtained from the arcuate nucleus and nucleus accumbens were 259.9 and 143.3 pM, respectively. Specific lesion of the serotonergic system by 5,7-dihydroxytryptamine (5,7-DHT) caused a significant decrease in these dialysate beta-endorphin levels. When 5-HT (0.25-5 microM) was added to the perfusion solution, the levels of beta-endorphin in the dialysate from the arcuate nucleus increased (186-296% of baseline), in a concentration-dependent manner. In the nucleus accumbens, 0.5 and 2 microM 5-HT in the perfusion fluid did not affect the levels of beta-endorphin in the dialysate, whereas 5 and 10 microM 5-HT caused an increase of approximately 190% of baseline. When fluoxetine (250 microM) was present in the perfusing solution, the levels of beta-endorphin in the dialysates from the arcuate nucleus and nucleus accumbens increased two- to threefold. This effect was not obtained in the 5,7-DHT-lesioned rats. Thus, 5-HT, either endogenously or exogenously delivered, appears to facilitate the release of beta-endorphin in the arcuate nucleus and nucleus accumbens. This indication of an interaction between serotonergic and endorphinic systems may be relevant for assessing pain and mood disorder circuits and the mode of action of antidepressant drugs.