Commentary

Presynaptic regulation of catecholamine release

The efficacy of perioperative dexmedetomidine (DEX) infusion as a precaution against postpartum depression (PPD) in women undergoing cesarean section has not been substantiated systematically. A literature search for RCTs on DEX against PPD was retrieved in the following databases from inception to January 3, 2024: PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, CBM, VIP, etc. A total of 13 RCTs with 1711 participants were included. Meta-analysis was performed by RevMan5.3 and Stata16 using a random-effects model. EPDS scores were significantly decreased in the DEX group within one week or over one week postpartum compared to the control group (SMD = −1.25, 95 %CI: −1.73 to −0.77; SMD = −1.08, 95 %CI: −1.43 to −0.73). The prevalence of PPD was significantly inferior to the control at both time points (RR = 0.36, 95 %CI: 0.24 to 0.54; RR = 0.39, 95 %CI: 0.26 to 0.57). Univariate meta-regression suggested that age influenced the heterogeneity of the EPDS scores (P = 0.039), and DEX infusion dose was a potential moderator (P = 0.074). The subgroup analysis results of PPD scores at both time points were consistent, showing that: ① Mothers younger than 30 years old had better sensitivity to DEX for treating PPD. ② The anti-PPD efficacy of continuous infusion of DEX by PCIA was superior to both single infusion and combined infusion. ③ DEX showed a better anti-PPD effect when the total infusion dose was ≤ 2 μg/kg. Moreover, DEX improved analgesia and sleep quality, provided appropriate sedation, and reduced the incidence of nausea, vomiting, and chills. The current evidence confirmed the prophylaxis and superiority of DEX for PPD. More high-quality, large-scale RCTs are required for verifying the reliability and formulating administration methods.

In the present studies, we assessed the effect of the 5-HT_1A receptor (R) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on motor and exploratory behaviors, object and place recognition and dopamine transporter (DAT) and serotonin transporter (SERT) binding in the rat brain. In Experiment I, motor/exploratory behaviors were assessed in an open field after injection of either 8-OH-DPAT (0.1 and 3 mg/kg) or vehicle for 30 min without previous habituation to the open field. In Experiment II, rats underwent a 5-min exploration trial in an open field with two identical objects. After injection of either 8-OH-DPAT (0.1 and 3 mg/kg) or vehicle, rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Subsequently, N-o-fluoropropyl-2b-carbomethoxy-3b-(4-[¹²³I]iodophenyl)-nortropane ([¹²³I]FP-CIT; 11 ± 4 MBq) was injected into the tail vein. Regional radioactivity accumulations were determined post mortem with a well counter. In both experiments, 8-OH-DPAT dose-dependently increased ambulation and exploratory head-shoulder motility, whereas rearing was dose-dependently decreased. In the test rial of Experiment II, there were no effects of 8-OH-DPAT on overall activity, sitting and grooming. 8-OH-DPAT dose-dependently impaired recognition of object and place. 8-OH-DPAT (3 mg/kg) increased DAT binding in the dorsal striatum relative to both vehicle and 0.1 mg/kg 8-OH-DPAT. Furthermore, in the ventral striatum, DAT binding was decreased after 3 mg/kg 8-OH-DPAT relative to vehicle. Findings indicate that motor/exploratory behaviors, memory for object and place and regional dopamine function may be modulated by the 5-HT_1AR. Since, after 8-OH-DPAT, rats exhibited more horizontal and less (exploratory) vertical motor activity, while overall activity was not different between groups, it may be inferred, that the observed impairment of object recognition was not related to a decrease of motor activity as such, but to a decrease of intrinsic motivation, attention and/or awareness, which are relevant accessories of learning. Furthermore, the present findings on 8-OH-DPAT action indicate associations not only between motor/exploratory behavior and the recognition of object and place but also between the respective parameters and the levels of available DA in dorsal and ventral striatum.

Serotonin(5-HT)ergic projections run from the raphe nuclei to dopamin(DA)ergic cells in substantia nigra/ventral tegmental area (SN/VTA) and to the terminal fields of DA neurons in nucleus accumbens, caudateputamen and neocortex. In the present studies, we assessed the effect of the 5-HT_1A receptor (R) antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarbox-amide maleate (WAY-100635) on motor and exploratory behaviors and on D_2/3R binding in the rat brain with in vivo imaging methods. D_2/3R binding was determined in the same animals after systemic application of WAY-100635 (0.4 mg/kg) and 0.9% saline (SAL), respectively, with [¹²³I]IBZM as SPECT ligand. Anatomical information for the delineation of the target regions was obtained with dedicated small animal MRI. Immediately after treatment with WAY-100635 or SAL, motor/exploratory behaviors were assessed for 30 min in two different batches of animals in an open field. WAY-100635 reduced D_2/3R binding in caudateputamen, thalamus, frontal cortex, parietal cortex and ventral hippocampus relative to SAL. Network analysis of regional binding data after WAY-100635 yielded positive connections between (1) caudateputamen and substantia nigra/ventral tegmental area, (2) caudateputamen and ventral hippocampus, (3) substantia nigra/ventral tegmental area and parietal cortex, (4) thalamus and dorsal hippocampus and (5) frontal cortex and parietal cortex, which were not present after SAL. Moreover, WAY-100635 decreased parameters of motor activity (overall activity, ambulation duration and frequency) but increased the duration of grooming behavior relative to SAL. The effect on exploration was time-dependent with an early increase and a subsequent decrease of behavioral parameters (rearing duration and frequency, frequency of head-shoulder motility). For WAY-100635, findings imply a region-specificity as well as a time-dependency of DAergic action.

While the favorable effect of adjuvant clonidine in the treatment of acute mania has been observed already about 40 years ago, this line of treatment has not been further investigated. Here, we resumed this topic, and we tested the effect of adjuvant clonidine, an antihypertensive stimulating the alpha-₂ central adrenergic receptor, on symptoms of mania, cognitive performance, and subjective sleep. To this end, we performed a randomized, double-blind and placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania.

A total of 70 inpatients (mean age: 37.40 years; 15.7% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant clonidine (0.2 mg/d to a maximum of 0.6 mg/d) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants’ cognitive performance was assessed at baseline and at day 24 at the end of the study.

Over time, mania scores significantly decreased (large effect size), but more so in the clonidine condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the clonidine, compared to the placebo condition (medium effect size). Over time, cognitive performance improved (medium effect size), irrespective from the study condition.

Compared to placebo, adjuvant clonidine to lithium improved symptoms of mania, as rated by experts’, and subjective sleep quality. Adjuvant clonidine had no further favorable (or detrimental) impact on cognitive performance.

The development of antidepressant drugs, in the last 6 decades, has been associated with theories based on a deficiency of serotonin (5-HT) and/or noradrenaline (NA) systems. Although the pathophysiology of major depression (MD) is not fully understood, numerous investigations have suggested that treatments with various classes of antidepressant drugs may lead to an enhanced 5-HT and/or adapted NA neurotransmissions. In this review, particular morpho-physiological aspects of these systems are first considered. Second, principal features of central 5-HT/NA interactions are examined. In this regard, the effects of the acute and sustained antidepressant administrations on these systems are discussed. Finally, future directions including novel therapeutic strategies are proposed.

This chapter draws attention to the historical perspective on the functions of the autonomic nervous system during exercise by normal and physically trained subjects. It also discusses the roles of the sympathetic and parasympathetic nervous systems in characterizing the cardiorespiratory responses to exercise. Moreover, the chapter focuses on selected ideas and the people contributing to the development, with a primary emphasis on dynamic exercise results from healthy populations. To understand the contributions of the sympathetic nervous system in an exercise response, it is necessary to identify the primary transmitter being released from sympathetic nerve endings and to perfect the measurement of epinephrine being released from the adrenal gland. History has shown that cardiovascular responses in humans are attenuated during moderate to heavy exercise with inhibition of ß-adrenoceptors. The chapter also provides minimal information on the ideas associated with the exciting and promising era of autonomic genomics.