AIMTo investigate the effect of 5-hydroxytryptamine (5-HT) on spontaneous unit discharges of primary somatosensory cortex (SI-SUD) and the role of 5-HT1A receptor in 5-HT inhibitory effect on SI-SUD in rat.

METHODSThe SI-SUD was recorded before and during microiontophoresis of 5-HT and 8-OH-DPAT (the selective agonist for 5-HT1A receptor. The changes of mean of interspike interval (MISI) of SI-SUD were analysed and handled with the statistics.

RESULTS(1) Effects of 5-HT on SI-SUD may be inhibitory (48/96), excitatory (26/96) or non-responsive (22/96), and the major effect is inhibitory. (2) In 20 of 5-HT inhibited units, 17 are also inhibited with microiontophoresis of 8-OH-DPAT, but 3 have no obvious response to 8-OH-DPAT.

CONCLUSIONThe major effect of 5-HT on SI-SUD is inhibitory. In majority of 5-HT inhibited units, 5-HT1A receptor may be existence, which may involve in the inhibition of 5-HT on SI-SUD.

8-Hydroxy-2-(di-n-propylamino)tetralin ; pharmacology ; Animals ; Female ; Male ; Rats ; Rats, Wistar ; Receptors, Serotonin ; drug effects ; physiology ; Serotonin ; physiology ; Somatosensory Cortex ; drug effects ; physiology

The present study was carried out to determine the role of 5-HT(1A) receptors in the generation and modulation of basic respiratory rhythm. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The medulla oblongata slice was prepared and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O2 and 5% CO2), and ended in 3 min. In cold MKS, a 600-700 microm single transverse slice was cut, which was rostral to the edge of area postrema and retained the hypoglossal nerve roots and some parts of the ventral respiratory group. The preparation was quickly transferred to a recording chamber and continuously perfused with carbogen-saturated MKS at a rate of 4-6 mL/min at 27-29 degrees C. Glass adsorb-electrodes containing Ag-AgCl needle were attached to the ventral roots of the hypoglossal nerve. Respiratory rhythmical discharge activity (RRDA) of the rootlets of hypoglossal nerve was recorded. Ten medulla oblongata slice preparations were divided into two groups. In group I, 5-HT(1A) receptor specific agonist (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OHDPAT, 20 micromol/L) was added into the perfusion solution for 10 min first, after washing out, the 5-HT(1A) antagonist [4-iodo-N-[2-[4-methoxyphenyl]-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride] (PMPPI, 10 micromol/L) was applied to the perfusion solution for 10 min. In group II, after application of 8-OHDPAT for 10 min, additional PMPPI was added into the perfusion solution for 10 min. The discharges of the rootlets of hypoglossal nerve were recorded. Signals were amplified and band-pass filtered (100-3.3 kHz). Data were sampled (1-10 kHz) and stored in the computer via BL-420 biological signal processing system. Our results showed that 8-OHDPAT increased the respiratory cycle (RC) and expiratory time (TE) as well as reduced the integral amplitude (IA), but the changes of the inspiratory time (TI) were not statistically significant. PMPPI induced a significant decrease in RC, TE and TI, but the changes of IA were not statistically significant. The effect of 8-OHDPAT on the respiratory rhythm was partially reversed by additional application of PMPPI. Taken together with previous results, 5-HT(1A) receptors may play an important role in the modulation of RRDA in the medulla oblongata slice preparation of neonatal rats.
8-Hydroxy-2-(di-n-propylamino)tetralin ; pharmacology ; Animals ; Animals, Newborn ; Medulla Oblongata ; physiology ; Piperazines ; pharmacology ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT1A ; physiology ; Respiration

The aim of the present study was to determine whether serotonergic drugs could reverse lipopolysaccharide (LPS) -induced anorexia in rats. LPS (500microgram/kg body weight) and all serotonergic drugs, except for 8-OH-DPAT (subcutaneous), were injected intraperitoneally into Sprague-Dawley rats. Without the LPS injection, 8-OH-DPAT (1A agonist), metergoline (1/2 antagonist), and mianserin (2A/2C antagonist) exerted no effects on food intake at any of the doses tested, but ketanserin (2A antagonist) caused an increase of food intake at 4 mg/kg. RS-102221 (2C antagonist) reduced food intake at 2 and 4 mg/kg. LPS reduced food intake 1 hour after injection, and food intake remained low until the end of measurement period (24 hours) (p< 0.05). Pretreatment of rats with 8-OH-DPAT partially recovered of cumulative food intake at all measured times (2, 4, 6, 8, and 24 hours after LPS injection). Pretreatment with metergoline resulted in a partial recovery of cumulative food intake at 2, 4, 6, and 8 hours, but not at 24 hours. Ketanserin caused partial recovery at 2 and 4 hours only. Mianserin and RS-102221 had no effects on LPS-reduced food intake. A variety of serotonergic drugs ameliorated anorexic symptoms, which suggesting that the serotonin system plays a role in LPS-induced anorexia.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Animals ; Anorexia* ; Diethylpropion ; Eating ; Ketanserin ; Metergoline ; Mianserin ; Rats* ; Rats, Sprague-Dawley ; Serotonin ; Serotonin Agents*

The role of 5-hydroxytryptamine (5-HT)1A receptor activity in prenatal ischemia was studied, by injecting 8-hydroxy-dipropylaminotetraline (8-OH-DPAT; 50 microgram/kg, s.c.), a 5-HT1A agonist on gestation day 17, and 30 min later inducing transient ischemia by ligating the uterine vessels for 30 min. On postnatal day 95, rats that had experienced prenatal ischemia showed impaired motor coordination and reduced concentration of 5-HT in the cerebellum compared with Sham-operated controls. In addition, they showed increased 5-HT1A receptor densities in the cerebral cortex. Pretreatment with 8-OH-DPAT ameliorated the behavioral and neurochemical sequelae measured in the present study. The results suggest that 5-HT1A receptors protect the brain from ischemic insult and/or facilitate recovery after prenatally experienced ischemia.
8-Hydroxy-2-(di-n-propylamino)tetralin* ; Animals ; Brain ; Cerebellum ; Cerebral Cortex ; Ischemia* ; Neuroprotective Agents* ; Pregnancy ; Rats* ; Receptor, Serotonin, 5-HT1A ; Serotonin ; Serotonin 5-HT1 Receptor Agonists

OBJECTIVETo investigate the effects of serotonin (5-HTIA) receptors in the hippocampal dentate gyrus (DG) on active avoidance learning in rats.

METHODSTotally 36 SD rats were randomly divided into control group, antagonist group and agonist group(n = 12). Active avoidance learning ability of rats was assessed by the shuttle box. The extracellular concentrations of 5-HT in the DG during active avoidance conditioned reflex were measured by microdialysis and high performance liquid chromatography (HPLC) techniques. Then the antagonist (WAY-100635) or agonist (8-OH-DPAT) of the 5-HT1A receptors were microinjected into the DG region, and the active avoidance learning was measured.

RESULTS(1) During the active avoidance learning, the concentration of 5-HT in the hippocampal DG was significantly increased in the extinction but not establishment in the conditioned reflex, which reached 164.90% ± 26.07% (P <0.05) of basal level. (2) The microinjection of WAY-100635 (an antagonist of 5-HT1A receptor) into the DG did not significantly affect the active avoidance learning. (3) The microinjection of 8-OH-DPAT(an agonist of 5-HT1A receptor) into the DG significantly facilitated the establishment process and inhibited the extinction process during active avoidance conditioned reflex.

CONCLUSIONThe data suggest that activation of 5-HT1A receptors in hipocampal DG may facilitate active avoidance learning and memory in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin ; pharmacology ; Animals ; Avoidance Learning ; Dentate Gyrus ; physiology ; Piperazines ; pharmacology ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT1A ; physiology ; Serotonin ; physiology ; Serotonin Receptor Agonists ; pharmacology

OBJECTIVETo investigate the role of 5-HT1A receptors in the generation and modulation of basic respiration rhythm.

METHODSBrainstem slices of 20 newborn SD rats (0-3 days) were prepared and respiratory rhythmical discharge activity (RRDA) of the hypoglossal nerve was recorded by suction electrode on these preparations including the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets retained, and the effects of 5-HT1A receptors on RRDA were investigated by application of specific agonist of 5-HT1A receptors 8-OH-DPAT in the perfusion solution. The 20 neonatal rats were divided into 4 groups and the brainstem slices were perfused continuously for 10 min with different concentrations of 8-OH-DPAT (1, 5, 10, 20 micromol/L, respectively). RRDA was recorded before and 1, 3, 5 min after 8-OH-DPAT perfusion.

RESULTSThe respiratory cycles (RC) varied significantly between the different time points of 8-OH-DPAT administration (F=181.219, P<0.001), which was the shortest before 8-OH-DPAT administration and increased progressively after administration till reaching the maximum 5 min after the administration. The RC also varied significantly between different 8-OH-DPAT concentrations (F=61.675, P<0.001). At each time point after 8-OH-DPAT administration, RC was the shortest with 1 micromol/L and maximum with 20 micromol/L 8-OH-DPAT. A crossover effect was observed between the time and administered 8-OH-DPAT concentration (F=22.940, P<0.001). The integrated amplitude (IA) was significantly different between different time points of 8-OH-DPAT administration (F=20.949, P<0.001), and the application of 10 and 20 micromol/L 8-OH-DPAT resulted in significant IA decrement (F=5.050, P=0.017; F=51.389, P=0.001, respectively). Different concentrations of 8-OH-DPAT also significantly affected IA (F=41.027, P<0.001), and at each time point after administration, IA was the maximum with 1 micromol/L and minimum with 20 micromol/L 8-OH-DPAT, also showing a crossover effect between time and 8-OH-DPAT concentration (F=3.483, P=0.002).

CONCLUSIONS8-OH-DPAT induces a dose-dependent increase in RC and a dose-dependent inhibition of the IA and burst frequency, with long-lasting inhibitory effect on the inspiration. 5-HT1A receptors play an important role in the modulation of the RRDA in isolated neonatal rat brainstem slice.

8-Hydroxy-2-(di-n-propylamino)tetralin ; pharmacology ; Animals ; Animals, Newborn ; Brain Stem ; drug effects ; physiology ; Dose-Response Relationship, Drug ; Electric Conductivity ; Electrophysiological Phenomena ; drug effects ; In Vitro Techniques ; Periodicity ; Rats ; Respiratory Mechanics ; drug effects ; physiology ; Time Factors

OBJECTIVE: Post weanling isolation-reared (IR) rats are featured with depressive phenotype, yet its mechanism is not clearly defined particularly in terms of the involvement of central 5-HT1A receptors. The present study aims to examine the effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT depletion. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14 days after the surgery, rats were assessed their performance in FST with or without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY). RESULTS: 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC rats. IR rats were more immobile and less sensitive to the lesion-induced immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7-DHT lesion increased the expression of PFC 5-HT1A receptors. CONCLUSION: The integrity of central 5-HT system is developmentally crucial for the 5-HT1A-relevant depression profile in rats of social isolation.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Amygdala ; Animals ; Depression* ; Hippocampus ; Phenotype ; Prefrontal Cortex ; Rats* ; Receptor, Serotonin, 5-HT1A ; Serotonin 5-HT1 Receptor Agonists ; Serotonin* ; Social Control, Formal ; Social Isolation

OBJECTIVE: Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT. Seven days later rats entered a protocol of 8-OH-DPAT, a 5-HT1A agonist, in which locomotor activity, ASR and PPI and their tissue levels of 5-HT were measured. RESULTS: Our results found that both IR and 5,7-DHT decreased the tissue concentration of 5-HT. IR-induced hyperactivity and gating impairment were unaffected by 5-HT depletion. 8-OH-DPAT strengthened the ASR in IR but not SOC rats and the drug-reduced PPI could be adjusted by 5,7-DHT pretreatment. 8-OH-DPAT at 100 μg/kg enhanced PPI in 5-HT-depleted SOC rats. However for IR rats, 8-OH-DPAT strengthened PPI in sham rats but downgraded it in depletion condition. CONCLUSION: The integrity of central 5-HT system is important to 5-HT1A-modulated sensorimotor gating in isolation-reared rats.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Acoustics ; Animals ; Motor Activity ; Prepulse Inhibition ; Rats ; Receptor, Serotonin, 5-HT1A ; Reflex, Startle ; Sensory Gating ; Serotonin ; Serotonin 5-HT1 Receptor Agonists ; Social Control, Formal

BACKGROUND AND PURPOSE: Neurobehavioral teratology is a term used for the postnatal effects on behavior of prenatal exposure to drug or to specific environment. Perinatal hypoxia is a major risk factor for development of behavioral abnormalities, such as cerebral palsy, mental retardation and learning disability. The objective of this study is to investigate the effects of neonatal hypoxia on long-term changes of behavior and neurochemical system and to learn the role of 5-hyroxytryptamine(5-HT) in hypoxic stress. METHODS: Sprague-Dawley rats were grouped by hypoxia and/or 5-HT receptor antagonist treatment. Exposure to 100% N2 gas was done in postnatal day(PND) 2 for 12 minutes. NAN-190 HBr or ketanserin tartrate or both were injected intraperitoneally 30 minutes before exposure to hypoxic environment. Rats were weighed periodically and examined the eye opening. Wire maneuver test was done on PND 22. Between PND 40-55 and PND 63-84, explorative behavior test and Rota-Rod test were done serially. They were sacrificed in PND 100, and aminergic neurotransimitters and their metabolites were measured by High Performance Liquid Chromatography - Electrochemical Detection(HPLC ECD) system. Receptor binding assay was done using 8-OH-DPAT and ketanserin HCl in brain cortex. RESULTS: The group treated with 5-HT receptor antagonist and hypoxia showed higher death rate than 5-HT receptor antagonist or hypoxia alone. There were no differences in weight gain, eye opening, and the result of wire maneuver test among each groups. In explorative behavior test, NAN+N2 group in male and NAN group in female showed markedly increased activities. In Rota-Rod test, NAN and NAN+N2 groups in both male and female showed decreased motor coordination. There were no differences in the concentration of aminergic neurotransmitters and their metabolites, when measured in PND 100 according to the brain sites. There were no differences in pKd of 5-HT receptors measured on PND 100. But Bmax of 5-HT1A receptor were low in N2, NAN and NAN+N2 groups. NAN and NAN+N2 groups showed elevated Bmax of 5-HT2A/2C receptor. CONCLUSION: Exposure to hypoxia in neonatal period causes long-lasting neurobehavioral changes with neurochemical abnormalities, and 5-HT receptor activity has a role in that mechanism.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Animals ; Anoxia ; Brain ; Cerebral Palsy ; Chromatography, Liquid ; Female ; Humans ; Infant, Newborn* ; Intellectual Disability ; Ketanserin ; Learning Disorders ; Male ; Mortality ; Neurotransmitter Agents ; Rats* ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT1A ; Receptors, Serotonin ; Risk Factors ; Serotonin ; Teratology* ; Weight Gain

Objective: To explore the feasibility and practicability of establishing a rat model of premature ejaculation (PE) by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord segments. METHODS: Twenty-four male Wistar rats were equally randomized into a PE model and a blank control group. The PE model was established by injection of 8-OH-DPAT in 10 ml normal saline at 0.8 mg per kg of the body weight per day into the subarachnoid space of the lumbosacral spinal cord segments and the control rats were injected with the same volume of normal saline only, both for 4 weeks. Another 24 female Wistar rats were injected subcutaneously with benzoic acid estradiol at 20 μg to induce estrus at 36 hours before mated with the male animals. At 2 and 4 weeks, the male rats were mated with the female ones for 30 minutes each time and meanwhile observed for their mating behavior indicators, such as mount latency, intromission latency, ejaculation latency, mount frequency, intromission frequency, and ejaculation frequency. RESULTS: Compared with the controls, the PE model rats showed a significantly lower ejaculation latency (［712.35 ± 36.77］ vs ［502.35 ± 46.72］ s, P<0.05), mount latency (［11.22 ± 3.60］ vs ［8.69 ± 2.48］ s, P<0.05), mount frequency (13.28 ± 0.24 vs 7.53 ± 1.84, P<0.05), and intromission latency (［22.33 ± 2.45］ vs ［12.08 ± 1.39］ s, P<0.05), but a remarkably higher ejaculation frequency (2.01 ± 0.48 vs 4.26 ± 0.89, P<0.05). No statistically significant difference was observed between the control and model animals in the intromission frequency (7.49 ± 2.21 vs 6.45 ± 1.89, P>0.05). CONCLUSIONS A rat model of premature ejaculation was successfully established by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord segments, which is of great significance for further study of the mechanism of premature ejaculation.
8-Hydroxy-2-(di-n-propylamino)tetralin ; administration & dosage ; Animals ; Benzoic Acid ; administration & dosage ; Disease Models, Animal ; Ejaculation ; Estradiol ; administration & dosage ; Estrus ; Feasibility Studies ; Female ; Injections, Spinal ; Male ; Premature Ejaculation ; chemically induced ; physiopathology ; Rats ; Rats, Wistar ; Sexual Behavior, Animal ; Spinal Cord ; Subarachnoid Space