Central nervous system activity of Rhazya stricta (Decne) in mice.

1. The effects of orally administered aqueous lyophilized extract of the leaves of Rhazya stricta (2, 4 & 8 g/kg) on aspects of nervous system function were investigated in mice. 2. In three antinociceptive tests (hot plate, abdominal constriction, and warm water tail flick tests), the extract exhibited dose-dependent and significant antinociceptive activity. Naloxone was ineffective in antagonizing the analgesic effect of Rhazya stricta on tail-flick and abdominal constriction tests, possibly indicating that this effect occurs via non-opiate pathways. 3.Pretreatment of mice with the xenobiotic metabolizing enzymes inhibitor cimetidine (50 mg/kg) did not significantly alter the antinociceptive action of the extract, indicating that the effect is probably due to the parent compound(s) present in the extract and not to metabolites thereof. 4. Rhazya stricta produce dose-dependent sedation, decreased motor activity, and impaired motor control. Time spent on a rotarod treadmill was significantly decreased after treatment with the extract. 5. Rhazya stricta extract (8 g/kg) produced a degree of sedation comparable to that produced by diazepam (5-10 mg/kg), and also significantly increased the reaction time of the tail-flick test, an action which was not produced by diazepam. 6. Administration of R. stricta extract potentiated pentobarbitone sleeping time in a dose dependent manner. The extract did not significantly antagonize picrotoxin induced convulsions. The extract (4 and 8 g/kg) significantly decreased the rectal temperature of normothermic and hyperthermic mice. 7. Pretreatment with R. stricta extract (8 g/kg) completely prevented the occurrence of aggressive behaviour in male mice. 8. It is concluded that the crude extract of R. stricta has central nervous system depressant properties.

Neurochemical transmission in the dorsal column nuclei.

The transmitter chemistry of the dorsal column nuclei is reviewed, with special emphasis on the monosynaptic component of the dorsal column-medial lemniscal pathway. It is maintained that in this anatomically addressed system concerned mainly with fast, secure sensory transmission, amino acids represent the predominant mechanism used for chemical relay of primary afferent impulses. The major excitatory primary afferent transmitter is most likely glutamic acid, whereas gamma-aminobutyric acid (GABA) fulfills adequately the role of transmitter of recurrent, postsynaptic and presynaptic inhibition. Recent immunohistochemical and physiological evidence indicates that 5-hydroxytryptamine, originating mainly from neurons of the raphé nuclei, plays a modulatory role in dorsal column transmission of innocuous sensory information. The basic synaptic elements involved in transmission across this relay, along with their corresponding chemical identities, are presented in the form of a speculative model.

Selective inhibition of nociceptive flexion reflex discharge by the kappa agonist bremazocine.

In unanaesthetized decerebrate spinal cats, bremazocine (0.012-0.2 mg/kg, i.v.) selectively inhibited the late C-fibre reflex discharge, recorded in sectioned lumbo-sacral ventral root filaments, after supramaximal electrical stimulation of the ipsilateral sural or common peroneal nerve. This action was naloxone-reversible. The results suggest that activation of kappa opioid receptors in the spinal cord inhibits the integration of nociceptive, but not locomotor, flexion reflexes.

Prolonged discharge of wide-dynamic-range spinal neurons evoked by formaldehyde injected in their cutaneous receptive fields.

In decerebrate, unanesthetized cats, subcutaneous injection of formaldehyde solutions (0.05 ml, 2.5%) in the receptive fields of spinal wide-dynamic-range neurons elicited an immediate and continuous discharge or burst activity in the neurons that lasted 10 to 55 min. This discharge was reduced by conditioning stimulation of the medial raphe nucleus and was completely abolished by morphine (3 mg/kg, i.v.). Low-threshold cutaneous mechanoreceptive neurons in the dorsal horn and dorsal column nuclei did not show a sustained response.

Inhibition of nociceptive evoked activity in spinal neurons through a dorsal column-brainstem-spinal loop.

In decerebrate-decerebellate cats, dorsal column stimulation (DCst), rostral to bilateral dorsal column cuts, inhibited dorsal horn neurons discharging to various types of nociceptive stimuli. Similar inhibitory effects were observed from conditioning nucleus raphe magnus stimulation. Activation of this dorsal column-brainstem-spinal loop could be part of an important supraspinal "gating' system to account for the alleviation of pain both by DCst and peripheral nerve stimulation in man.

Dorsal column input to inferior raphe centralis neurons.

In anesthetized decerebellate cats with additional decerebration or decortication and with one of two types of cervical spinal lesions which either eliminated the dorsal half of the spinal cord or spared the dorsal funiculi, peripheral electric and localized natural stimuli activated neurons in the inferior raphe nuclear complex. Medial lemniscal as well as direct dorsal funicular stimulation was also effective. The majority of raphe neurons activated by stimulation of the dorsal funiculi were also discharged by ventrolateral funicular stimulation.

Modification of transmission in the cuneate nucleus by raphe and periaqueductal gray stimulation.

In anesthetized decerebellate cats, with additional decerebration or decortication and with one of two types of cervical spinal cuts which either eliminated the dorsal half of the spinal cord or spared the dorsal funiculi, conditioning stimulation in the raphe nuclei or periaqueductal gray modified transmission in the cuneate nucleus. This was shown by 4 types of recordings: surface potentials, somatic afferent excitability testing, lemniscal tract response and extracellularly recorded single neuron activity.

Enhancement by pyridoxine of the action of diazepam on spinal presynaptic inhibition.

In spinal unanesthetized cats, pyridoxine pretreatment significantly enhanced the diazepam-induced increase in dorsal root potentials and dorsal root reflexes.

Antagonism of the spinal action of diazepam by semicarbazide.

In spinal unanaesthetized cats, pretreatment with semicarbazide (200 mg/kg) 2-4.5 h prior to the administration of diazepam (1-4 mg/kg) completely blocked the enhancement of the segmental dorsal root reflex by the latter compound. Pyridoxine hydrochloride (200 mg/kg), given 3.5 h after semicarbazide, restored the spinal effect of diazepam administered 1 h later. The possibility of a link between diazepam and spinal gamma-aminobutyric acid is suggested and discussed.

Polysensory interactions in the cuneate nucleus.

1. The effects of light flashes or sound clicks on somatic sensory activity in the cuneate nucleus of the cat were studied. Polysensory interactions were demonstrated by means of gross potential recording in the cuneate nucleus or medial lemniscus, single unit recording in the cuneate nucleus, and excitability testing of tract terminals.2. Brief flashes or clicks were found to produce negative (N) and positive (P) waves in the cuneate nucleus similar to those produced by cutaneous stimulation. Furthermore, the P wave evoked by conditioning photic or acoustic stimuli depressed the P wave produced by cutaneous test stimuli.3. Conditioning photic or acoustic stimuli inhibited spontaneously firing cuneate neurones as well as those driven by cutaneous test stimuli.4. Conditioning photic or acoustic stimuli depressed the test discharge in the medial lemniscus evoked by cutaneous test stimuli.5. Micro-electrode stimulation within the cuneate nucleus evoked an antidromic response in the superficial radial nerve consisting of two spike complexes. Conditioning photic or acoustic stimuli caused an increase in the size of the initial spike complex and a depression in the secondary spike complex. These changes and the time courses of all the interactions observed were suggestive of presynaptic inhibition.6. The modulatory influences of photic and acoustic stimuli on the cuneate nucleus were present under alpha-chloralose or pentobarbitone anaesthesia and the acoustic influence persisted after midcollicular decerebration. When added to other evidence, the above findings suggest that the reticular formation of the brain stem plays an important role in these polysensory interactions.