Serotonergic mechanism in imipramine induced antinociception in rat tail flick test.

Substantial evidence has accumulated that spinally projecting serotonergic neurons modulate nociception. However, the exact receptor subtypes that mediate the antinociceptive response of serotonin within the spinal cord continue to be a subject of debate. Therefore, we explored the effect of serotonergic system on imipramine induced antinociception by using 5-Hydroxytryptamine-3 (5HT3) receptor antagonist ondansetron and 5-Hydroxytryptamine-2 (5HT2) receptor antagonist mianserine, and depletion of brain 5-Hydroxytryptamine (5HT) with p-chlorophenyl alanine (PCPA). Male wistar strain rats were pretreated with either ondansetron (0.5 mg/kg, i.p.) or mianserine (1 mg/kg, i.p.). After 15 minutes, rats received injection of imipramine (10 mg/kg). Nociception was assessed by tail-flick method. Imipramine (2 mg, 5 mg, 10 mg, and 20 mg/kg) produce antinociceptive response in the dose dependent manner. Prior treatment with 5HT3 antagonist, Ondansetron and 5HT2 antagonist, mianserine reduce the antinociceptive response of imipramine. In PCPA treated rats imipramine (10 mg/kg) failed to produce antinociception. These results indicate that the 5HT plays an important role in imipramine induced antinociception.

Effects of p-chlorophenylalanine-induced depletion of brain serotonin on retrieval of appetitive and aversive memories.

This study examined whether depletion of central serotonin produces an improved retrieval of aversive memories in the same way as pre-exposure to inescapable footshocks, in rats. Animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were given i.c.v. 24 hr later a single dose of p-chlorophenylalanine (p-CPA). (100, 200, 400 micrograms/rat) or drug vehicle. The retention performance and activity were assessed 48 hr after treatment with this depletor. While lower doses of p-CPA selectively reduced serotonin levels in striatum and anterior cortex, higher doses reduced both serotonin and norepinephrine levels in hippocampus in a dose-dependent fashion. The depletor however, failed to produce a differential improvement of aversive memory retrieval. On the contrary, p-CPA reduced the latency to enter both, previously shocked and appetitively reinforced, goalboxes. The enhanced traversing behaviour in T-maze, together with an increased central entry in the open field that observed in depleted groups, might suggest an anxiolytic activity of p-CPA.

A functional interaction between GABA and 5-HT in inhibiting picrotoxin-induced myoclonus in rats.

Pretreatment with 5-hydroxytryptophan (5-HTP), a precursor of 5-HT, antagonised while pretreatment with p-chlorophenylalanine (PCPA), a 5-HT depletor, potentiated the myoclonus induced by picrotoxin, a GABA antagonist. Pretreatment with aminooxyacetic acid (AOAA), a GABA transaminase inhibitor, antagonised picrotoxin-induced myoclonus. The combined effect of the least protective doses of AOAA and 5-HTP was greater than the sum of their individual inhibitory effects on picrotoxin-induced myoclonus. Further, AOAA failed to inhibit picrotoxin-induced myoclonus in PCPA pretreated rats. These findings suggest that the central 5-HT-ergic system exerts a facilitatory influence on the GABA-ergic system and thus it is involved in the antimyoclonic action of GABA.

Acute neurobehavioural toxicity of phosphamindon and its drug-induced alteration.

Phosphamidon, a systemic organophosphate insecticide, (1.4 mg/kg - dose 1/4th of LD50 given ip), produced several autonomic, neurological and behavioral effects in mice with peak effects being at 15 min. Similar dose in rats also abolished conditioned avoidance response. Pre-treatment with atropine, iproniazid, alpha-methyl-p-tyrosine, p-chlorophenylalanine or thiosemicarbazide reduce many of these effects. This suggests that phosphamidon toxicity involves the central cholinergic, adrenergic, serotonergic and GABAergic systems in addition to peripheral cholinergic effects.

Influence of 6-hydroxydopamine on ethanol narcosis in mice

Se estudian los efectos de la administración de 6-hidroxidopamina (6-OHDA0, 100 Y 200 microng i.c.v., en la duración de la narcosis por etanol en ratones sin o con tratamiento de alfa-metil-p-tirosina (AMPT), p-cloro-fenilalanina (PCPA) o 5-hidroxitriptófano (5-HTP). La narcosis por etanol fue significativamente más prolongada en los ratones que recibieron 200 microng de 6-OHDA i.c.v. que en los testigos. La duración de la narcosis en los ratones tratados con ambas dosis de 6-OHDA fue significativamente más larga cuando éstos recibieron previamente AMPT (inhibidor de la biosíntesis de seotonina). En 5-HTP (precursor de la biosíntesis de serotonina). En cambio, en los pretratados con PCPA (inhibidor de la triptófano hidroxilasa), la 6-OHDA no modificó la duración de la narcosis por etanol. Las alcoholemias al momento de despertar no cambiaron significativamente por la 6-OHDA. Estos resultados son consistentes con la hipótesis de que la disminución de noradrenalina así como el aumento de serotonina cerebrales prolongan la narcosis por etanol y, en cambio, el aumento de noradrenalina o la disminución de serotonina en el cerebro reducen la narcosis por etanol

Participaçäo da serotonina na hipertermia desencadeada por lesäo eletrolítica mesencefálica em ratos / Participation of serotonin in the hyperthermia induced by mesencephalic electrolytic in rats

O presente estudo tentou determinar o papel da serotonina na etiologia de uma elevaçäo anormal da temperatura corporal observada em ratos após a lesäo eletrolítica feita nas áreas dorsais do mesencéfalo. A hipertermia observada mostrou ser bloqueada pela administraçäo prévia de para-clorofenilalanina, um inibidor da síntese de serotonina. Estes resultados reforçam a sugestäo de que a lesäo eletrolítica desencadeia uma atividade irritativa das vias serotoninérgicas, que ascendem próximas ao local da lesäo, ativando os mecanismos termogênicos

Involvement of a serotonergic control in the regulation of plasma levels of immunoreactive beta-endorphin

Se midió la concentración de beta-endorfina inmunoreactiva (B-E i.r.) en plasma e hipotálamo de ratas tratadas con alfa-metil-p-tirosina ( alfa -MT) (dos dosis de 200 mg/kg) o p-cloro-fenil-alanina (PCPA) (dos dosis de 150 mg/kg). Se determinó además la concentración de B-E i.r. en plasma después de una única dosis (5 mg/kg) de anfetamina o luego de la estimulación eléctrica del núcleo mediano del rafe (NMR). Los niveles plasmáticos de B-E i.r. disminuyeron por la administración de PCPA o aumentaron por la estimulación eléctrica del NMR. Tanto la adminsitración de alfa -MT como la de anfetamina fue inefectiva en modificar la concentración plasmática de B-E i.r. Los resultados sugieren un papel para la serotonina en la regulación del nivel plasmático de B-E i.r.

Role of 5-HT on increased permeability of blood-brain barrier under heat stress.

Exposure of young rats (9-10 wks) to chronic summer heat (36 degrees C) or acute heat (38 degrees C 4hr) increased the BBB permeability to Evans blue albumin complex (MW 68,000) and 131I-sodium (MW 154) in different brain regions which correlated well with the increased level of 5-HT in plasma and brain. This increased permeability of BBB and the increased 5-HT level were prevented by pretreatment with p-CPA, indomethacin and diazepam. Cyproheptadine and vinblastine pretreatment however, prevented only the increased permeability of BBB, the plasma and brain 5-HT level continued to remain high. These results indicate a probable role of 5-HT as one of the factors leading to the increased permeability of BBB in young rats following heat stress.

Effect of restraint stress on cannabis-induced catalepsy in rats.

The effect of restraint stress (1, 2 and 4 hr) on cannabis-induced catalepsy, was investigated in rats. Restraint stress produced a time-related-potentiation of the cataleptic effect of a sub-cataleptic dose of cannabis. Stress (4 hr)-induced potentiation of cannabis catalepsy was attenuated after pretreatment of the animals with drugs known to decrease central 5-HT and prostaglandin activity, but was unaffected by metyrapone, an inhibitor of endogenous corticoid synthesis. The results suggest the involvement of 5-HT and prostaglandins in restraint stress-cannabis interaction. The results have been discussed in the light of earlier investigations, from this laboratory, indicating increased rat brain 5-HT and prostaglandin activity, following restraint stress, and possible 5-HT mediation in central effects of prostaglandins. It is suggested that restraint stress first enhances rat brain prostaglandins, which in its proposed role as the first mediator' of stress, activates the serotonergic system in this species. This prostaglandin 5-HT link, thus mediates the observed potentiating effect of restraint stress on cannabis catalepsy.