Monoaminergic mediation of masculine and feminine copulatory behavior in female rats.

Ovariectomized rats treated with testosterone propionate (TP; 100 mug/kg X 6 days) and para-chlorophenylalanine (pCPA; 100 mg/kg X 3 days), a serotonin synthesis inhibitor, showed more masculine copulatory behavior (including the ejaculatory pattern) than did females receiving either TP or pCPA alone. The facilitatory effect of pCPA on the masculine copulatory behavior in females was not potentiated by pargyline (50 or 100 mg/kg), a monoamine oxidase inhibitor; instead, pargyline antagonized the effect of pCPA. Apomorphine (100 mug/kg), a dopamine receptor stimulant, did not increase masculine copulatory behavior in TP treated females. Adopaminergic facilitatory effect was therefore not demonstrated. These results suggest a serotonin-mediated inhibition of masculine copulatory behavior in female rats. When feminine copulatory behavior was tested, females receiving TP plus pCPA plus pargyline, TP plus pargyline, or TP plus apomorphine displayed lordosis in response to mounting by male rats. Lordosis did not occur after administration of TP, PCPA, or pargyline, individually or in any other combination. The responses in pargyline groups are consistent with the hypothesis of a noradrenergic facilitatory system for lordotic behavior. The responses in the apomorphine group are discussed in terms of a possible role for low level dopaminergic stimulation in facilitating lordosis.     

Reinstatement of LH surges by serotonin neuroleptics in aging, constant estrous rats

Aged rats in constant estrous (CE) were treated with drugs which effect monoamine metabolism in an attempt to restore the positive-feedback response to estrogen. Prior to treatment, the rats were ovariectomized so as to eliminate indirect effects of drug: ovary interaction which might alter the steroid environment. They then received silastic capsules containing estradiol 17β, SC, immediately (IME, immediate implant group) or 4 weeks after surgery (DEL, delayed implant group), to provide a constant, stable source of estrogen, mimicking the CE condition. Blood samples were taken 3 days after estrogen capsules were implanted to determine if the exogenous steroid induced LH surges in IME or DEL rats. LH surges occurred in 80% of DEL rats, but no IME rats suggesting that a 30-day hiatus from ovarian steroids restored the positive-feedback response in previously acyclic rats. Progesterone (0.5 mg) administered at 1100 hr increased the size of the surge in DEL rats but did not change serum LH levels in IME rats. After 3 days of estrogen exposure, hypothalamic content of serotonin was significantly lower (p <0.05) in DEL rats vs. IME rats, while norepinephrine was not different in either group. Differential effects of estrogen on norepinephrine were not apparent in IME or DEL rats. The changes in serotonin metabolism following estrogen treatment in DEL rats occurred with the onset of LH surges, suggesting a functional correlation. On the other hand, serotonin levels did not change in response to estrogen in IME rats, and LH surges were absent as well. Monoamine neuroleptics were administered to IME rats in an attempt to reestablish positive feedback. I-Dihydroxyphenylalanine (l-DOPA; 200 mg/kg at 1100 hr) stimulated LH surges in 31% of the rats; however, its effectiveness was diminished (8% responding with LH surges) by pretreatment with p-chlorophenylalanine (pCPA; 250 mg/kg at 1600 hr, 19 hours before l-DOPA). LH surges were reinstated in the majority (77%) of IME rats following combined treatment with pCPA + 5-hydroxytryptophan (5-HTP; 50 mg/kg at 1100 hr, 43 hours after pCPA). Since this combination of pCPA + 5-HTP enhances sensitivity to serotonin signals, the drugs may have restored the facilitatory effect of serotonin on LH secretion which is lost in aging constant estrous rats. In conclusion, loss of the positive-feedback response in aging female rats may follow changes in monoamine metabolism resulting from life-long exposure to estrogen. Although metabolic changes occur in all hypothalamic monoamines, this study suggests that a major deficit with regard to this feedback loss residues with serotonin.     

Effects of para-chlorophenylalanine and 5-hydroxytryptophan on alcohol intake in the rat

Para-chlorophenylalanine, the tryptophan hydroxylase inhibitor that depletes serotonin selectively, increased alcohol intake in rats. 5-Hydroxytryptophan, the serotonin percursor, reduced alcohol intake. These findings suggest that alcohol preference in the rat may be related to the brain tryptaminirgic system.     

Transient receptor potential vanilloid 4–expressing macrophages and keratinocytes contribute differentially to allergic and nonallergic chronic itch

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Involvement of serotonergic system in the antidepressant-like effect of piperine

Piperine is a major alkaloid of black pepper (Piper nigrum Linn.) and long pepper (P. longum Linn.), and its antidepressant-like effect has been previously demonstrated. The purpose of this study was to explore the possible contribution of the serotonergic system in the antidepressant-like effect of piperine in mice. The results showed that piperine significantly reduced the immobility time in the forced swim test and tail suspension test in mice. The anti-immobility effect of piperine in the forced swim test and tail suspension test was completely abolished by pre-treating the mice with pCPA (an inhibitor of 5-HT synthesis). Piperine treatment also significantly potentiated the number of head-twitches of mice induced by 5-HTP (a metabolic precursor to 5-HT). In addition, the neurochemical assays showed that piperine produced a marked increase of 5-HT level in both the hippocampus and frontal cortex of mice. Taken together, these results clearly suggest that the antidepressant-like effect of piperine is mediated via the serotonergic system by enhancing 5-HT content in mouse brain.     

Potentiating effects of L-type Ca2+ channel blockers on pentobarbital-induced hypnosis are influenced by serotonergic system

Summary. In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca²⁺ antagonists, the effects of three structurally diverse types of Ca²⁺ antagonists combined or not with 5-HT on pentobarbital-induced hypnosis in mice were investigated. The results showed that dihydropyridine derivative nifedipine (10.0 and 20.0 mg/kg, p.o.) and other types of Ca²⁺ antagonist, verapamil (5.0 and 10.0 mg/kg, p.o.) and diltiazem (2.5, 5.0 and 10.0 mg/kg, p.o.) increased both the sleeping time in hypnotic dosage of pentobarbital (45 mg/kg, i.p.) treated mice and the rate of sleep onset in the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.) treated mice in a dose-dependent manner, respectively, and these effects were significantly augmented by 5-hydroxytryptophan (5-HTP), the immediate precursor of 5-hydroxytryptamine (5-HT). Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleeping time and nifedipine (10.0 mg/kg, p.o.), verapamil (5.0 mg/kg, p.o.) and diltiazem (2.5 mg/kg, p.o.) abolished this effect. From these results, it should be presumed that the augmentative effect of L-type Ca²⁺ channel blockers on pentobarbital-induced sleep may be influenced by serotonergic system.     

Ipsapirone and 8-OH-DPAT reduce ethanol preference in rats: involvement of presynaptic 5-HT1A receptors

The selective serotonin(5-HT)_1A receptor agonists 8-OH-DPAT and ipsapirone were tested in selectively inbred Wistar rats, with high preference [70–90%: defined as the ratio of ethanol (EtOH) to total fluid intake] for EtOH (10% v/v) over water in a two-bottle free choice situation. Rats were injected shortly before the overnight test session (8:00p.m.–8:00a.m.). EtOH and water consumption were determined in 20-min intervals; food consumption after the session. 8-OH-DPAT (ED₅₀: 2.4 mg/kg, SC) and ipsapirone (ED₅₀: 12.5 mg/kg, SC) reduced EtOH preference in a dose-dependent manner. In addition, 8-OH-DPAT increased total fluid intake, whereas ipsapirone enhanced total food intake. The EtOH preference reduction was time-dependent and reached a maximum within the second 4 h after application of 8-OH-DPAT (–73%) and ipsapirone (–72%). The preference reducing effect of ipsapirone (20 mg/kg, PO) was completely blocked by the nonselective 5-HT_1A antagonist spiperone (0.05 mg/kg, SC). Local application of 8-OH-DPAT (10 µg, 0.5 µl) into the dorsal raphe nucleus (DRN, a brain area rich in somatodendritic 5-HT_1A autoreceptors), reduced the EtOH preference significantly as compared to the saline injection in the same animal (–12%, 8:00–12:00p.m.). Only marginal effects on ingestion behavior were observed after micro-injection into the nucleus accumbens. Reduction of brain 5-HT levels by pretreatment with the 5-HT synthesis inhibitor pCPA (2×150 mg/kg, IP) resulted in a short lasting, marked reduction (–54%) and a long lasting, small attenuation of the EtOH preference. Total food consumption was strongly decreased but returned soon to normal; total fluid intake was only slightly decreased. The EtOH preference reducing effect of ipsapirone (5 and 20 mg/kg, SC) was attenuated in pCPA-pretreated rats. The present data suggest that 5-HT_1A receptor ligands reduce EtOH preference via stimulation of 5-HT_1A receptors in the DRN. The possibility of additional mechanism(s) is discussed.     

Immunohistochemical localization of putative neurotransmitters within the feline nucleus tractus solitarii

With the aid of immunohistochemical techniques the distribution of substance P, met-enkephalin, serotonin, somatostatin, alpha-melanocyte stimulating hormone, neurotensin and neurophysin immunoreactivities were mapped throughout the rostro-caudal extent of the cat's nucleus tractus solitarii. Three of the putative neurotransmitters (substance P, enkephalin and serotonin) were found to be widely distributed as varicose fibers and punctate structures. The densities of their immunoreactivities were plotted in a range from very dense, dense, moderate, occasional, to none, at different levels of the nucleus of the solitary tract. Substance P immunoreactivity was the most varied and dense of all the neurotransmitters studied. Its accumulations ranged from very dense in the lateral, dense in portions of the parvocellular and lateral, moderate in medial and commissural and occasional in ventrolateral and portions of the parvocellular subdivisions. Both the enkephalin and serotonin immunoreactivities had patterns similar to that of substance P immunoreactivity, although their amounts were not as great. Following colchicine treatment neurons containing substance P and enkephalin immunoreactivity were found in many subdivisions of the nucleus of the solitary tract. Somatostatin, alpha-melanocyte stimulating hormone, neurotensin and neurophysin immunoreactivities were present in the nucleus of the solitary tract as isolated varicose fibers scattered throughout the nucleus. Immunoreactive neurons were not found for these putative neurotransmitters after colchicine treatment. The presence of substance P immunoreactivity within subdivisions which receive visceral afferent input is discussed in relation to the role of substance P as a possible transmitter of the afferent limb of the vagus nerve. The distribution of enkephalin and serotonin immunoreactivities in the nucleus of the solitary tract reflect their involvement in the regulation or modulation of cardiovascular and respiratory functions. While the significance of somatostatin, alpha-melanocyte stimulating hormone, neurotensin and neurophysin immunoreactivities within the nucleus of the solitary tract is not understood at present, these substances might possibly play a role in visceral functions.     

延髓中缝核5-羟色胺对清醒大鼠胃运动的影响

本工作采用应力传感器记录胃窦的运动,观察向清醒大鼠延髓中缝核注射1微升生理盐水中含6.25μg、12.5μg和25μg三种不同剂量的5-羟色胺(5HT)以及腹腔注射对氯苯丙氨酸(pCPA)或延髓中缝核注射5,6-双羟色胺(5,6DHT)以减少内源性5HT对胃运动的影响。实验结果表明:6.25μg 5HT有兴奋胃窦运动的趋势,12.5μg和25μg 5HT使胃窦收缩活动加强。将上述三种剂量的5HT注入外周静脉均不影响胃的运动。腹腔注射pCPA后第四天和延髓中缝核注射5,6DHT后第五天,抑制大鼠胃运动。此时,颈髓、延髓、中桥脑、间脑5HT含量均明显下降。提示延髓中缝核5HT参与胃运动的中枢性调节。     

Antidepressant-like effect of Valeriana glechomifolia Meyer (Valerianaceae) in mice

The antidepressant-like effect of a supercritical CO₂ (SCCO₂) Valeriana glechomifolia extract enriched in valepotriates was investigated in a mice tail suspension test (TST) and forced swimming test (FST). The SCCO₂ extract decreased mice immobility in the FST (0.5-20 mg/kg p.o.) and elicited a biphasic dose-response relationship in the TST (1-20 mg/kg p.o.) with no alterations in locomotor activity and motor coordination (assessed in the open-field and rota-rod tests, respectively). The anti-immobility effect of the SCCO₂ extract (5 mg/kg, p.o.) was prevented by mice pre-treatment with yohimbine (1 mg/kg, i.p., an α2 adrenoceptor antagonist), SCH 23390 (15 μg/kg, s.c., D₁ dopamine receptor antagonist) and sulpiride (50 mg/kg, i.p., D₂ dopamine receptor antagonist). However, mice pre-treatments with prazosin (1 mg/kg, i.p., α1 adrenoceptor antagonist) and p-chlorophenilalanine methyl ester (4 × 100 mg/kg/day, i.p., a serotonin synthesis inhibitor) were not able to block the anti-immobility effect of the SCCO₂ extract. Administration (p.o.) of the SCCO₂ extract (0.25 mg/kg) and imipramine (10 mg/kg), desipramine (5 mg/kg) and bupropion (3 mg/kg) at sub-effective doses significantly reduced mice immobility time in the FST. These data provide the first evidence of the antidepressant-like activity of V. glechomifolia valepotriates, which is due to an interaction with dopaminergic and noradrenergic neurotransmission.