Habenulo-interpeduncular lesions: the effects on pain sensitivity, morphine analgesia and open-field behavior in rats.

The lesions of medial habenular nuclei increased the pain sensitivity, enhanced the analgesic activity of morphine and slightly activated the behavior. The lesion of fasciculus retroflexus, a pathway connecting habenular nuclei with interpeduncular nucleus enhanced the pain sensitivity less markedly, did not change the efficacy of morphine analgesia, but significantly increased the activity of animals. The lesion of interpeduncular nucleus influenced the pain sensitivity to a smallest degree, did not change the analgesic activity of morphine, but dramatically increased the activity of animals. The activation did not resemble the aimless excitation of amphetamine-treated or raphe-lesioned rats, and no signs of increased emotionality or irritability were noted. The results are interpreted as an evidence of habenulo-interpenduncular complex being a part of a system, involved in the regulation of behavioral activity and the sensitivity to the aversive stimuli. These functions are in all probability mediated partly through substance P and met-enkephalin containing neurons, present in these structures.

Substance P, hexapeptide pGlu6(SP6-11), analgesia and serotonin depletion.

Substance P caused marked analgesic activity in rats after intraventricular administration and in mice after intraperitoneal injection. The hexapeptide pGlu6(SP6-11) was active in mice, but not in rats. Depletion of serotonin with p-chlorophenylalanine abolished the antinociceptive activity in mice, but not in rats, whereas lesion of raphe nuclei blocked the activity of substance P in the latter animals. Although different routes of administration were used, the results seem to indicate different mechanisms of analgesic activity of both peptides in rats and mice, as well as the different role of serotonergic transmission in pain control mechanisms in both species.

Modification of cholinergic tremor by apomorphine and L-dopa in rats.

Pretreatment with apomorphine, increased and prolonged the arecoline-induced tremor in rats. When given before pilocarpine, it produced different effects dependent on the dose: low doses (0.05 and 1.0 mg/kg) antagonized, but higher doses (5.0 and 10.0 mg/kg) enhanced the pilocarpine tremor. The extent and duration of arecoline tremor after pretreatment L-DOPA increased significantly, but this was not observed in the pilocarpine-induced tremor. These results suggest that the relations between striatal dopaminergic and cholinergic systems may be complex and the model based on a simple antagonism between these systems may be oversimplified.

Lesion of locus coeruleus: the effect on pethidine and pentazocine analgesia.

Analgesic activity of pethidine and pentazocine in the locus coeruleus lesioned rats was evaluated. Bilateral destruction of locus coeruleus resulted in a marked decrease in noradrenaline content in forebrain but did not change significantly the levels of dopamine. Lesioned animals showed a marked decrease of predrug pain threshold. However, pethidine increased more effectively the nociceptive threshold in lesioned rats. The effect observed after pentazocine was generally similar but the maximal increase in pain threshold in lesioned animals did not differ significantly from the values observed in sham lesioned rats. The action of both analgesics was markedly prolonged after the lesion of the locus coeruleus.

The effects of lesion of mesolimbic dopamine neurons on pain threshold and morphine analgesia in rats.

Lesions of ventral tegmental area, localised in the region of A 10 group of dopaminergic mesolimbic neurons decreased the pain threshold in rats. The absolute threshold values in morphine treated animals with the above lesion were lower than in sham-operated controls, however, the thresholds expressed as percentage of predrug threshold values did not differ in both lesioned and sham-operated animals. It is thought, that lesions of ventral tegmental dopamine neurons decrease the pain threshold due to the increase of general excitability of animals, and that there is no direct involvement of the lesioned structure in the primary mechanism of morphine analgesia.

Central anticholinergic effects of N-ethyl-2-pyrrolidylmethyl-cyclopentylphenyl glycollate.

The following effects of N-ethyl-2-pyrrolidyl-methyl-cyclopentylphenyl glycollate (PMCG) have been studied: effects on aggressive behaviour in mice and on general behaviour in rats, protective effects against central action of arecoline and nicotine in mice, thermo-regulatory effects in mice, protective action in poisonings with fluostigmine in mice and rats, and effects on bioelectrical activity of the brain in cats. It was stated that PMCG possesses a strong central anticholinergic activity blocking predominantly central muscarinic receptors; PMCG had also strong protective effects in anticholinesterase intoxications. It is suggested that this drug could have antiemotional and antiparkinsonian properties.

Papaverine, drug-induced stereotypy and catalepsy and biogenic amines in the brain of the rat.

The effects of papaverine on haloperidol-induced catalepsy and apomorphine-induced stereotypy as well as brain monoamines concentrations in rats were studied. Papaverine increased cataleptogenic effect of haloperidol whilst reduced stereotypy induced by apomorphine. Slight but significant decrease in brain dopamine concentration was observed in rats treated with papaverine. The present study indicates that papaverine has influences upon dopaminergic mechanisms in the brain.

Further study on pharmacology of meclophenoxate and it components in mice.

The effects of three-day treatment with meclophenoxate (Centrophenoxin) and its components, p-chlorophenoxyacetic acid and dimethylaminoethanol, on the aggressiveness and pain threshold in mice were investigated. p-Chlorophenoxyacetic acid increased the aggressiveness and pain sensitivity. Dimethylaminoethanol, on the contrary, tended to decrease these items of behaviour. The effects of meclophenoxate reflected this reciprocal activity of components, the activity of p-chlorophenoxyacetic acid prevailing. The results are taken as the evidence of some slowly developing mechanism in the activity of p-chlorophenoxyacetic acid, responsible for some of the effects of meclophenoxate. A possible mode of action of p-chlorophenoxyacetic acid is suggested.