Modifications in avoidance reactions of mice, on a second exposure to the hot plate, resist to various amnesia-inducing treatments.

The avoidance responses of mice exposed to the hot plate (55 degrees C) were found to be modified when tested a second time. In fact, when forepaws licking was no longer observed, the rearing was clearly anticipated (7 s instead of 15 s) as well as jumping (24 s instead of 55 s). These modifications of avoidance strategies as well as their latencies were still observed even 24 days after the first exposure.

Proerectile effects of apomorphine in mice.

Dopaminergic pathways play a key role in the central control of sexual behavior. Stimulation of central dopaminergic receptors elicits penile erection in a variety of species and has been proposed as a treatment option for erectile dysfunction in humans. The present study investigated the proerectile effects of apomorphine in mice.

Evidence for a localization of [(3)H]nociceptin binding sites on medullar primary afferent fibers.

The ORL1 receptor (opioid receptor-like 1) and its endogenous ligand, nociceptin, are involved in nociperception. We have studied, in a deafferented animal model, the modification of medullar [(3)H]nociceptin binding site density. A rhizotomy was carried out in rats at the cervicothoracic level, and the dorsal afferent fibers from C5 to T1 were lesioned.

Mouse lines differing in sensitivity to beta-CCM differ in tasks used for testing antidepressants.

Two lines of mice, previously selected for their sensitivity (BS) or their resistance (BR) to an anxiogenic benzodiazepine (BZ) receptor inverse agonist, methyl beta-carboline-3-carboxylate (beta-CCM), have recently been shown to present several differences in anxiety. In the present study, attempt was made to extend their behavioral profile in two situations classically used for testing antidepressant drugs. Reassessment of locomotor performance of these new populations confirmed that the motor activity of BR mice was lower than that of BS mice.

Divergent levels of anxiety in mice selected for differences in sensitivity to a convulsant agent.

Spontaneous behavior patterns were assessed in eight different behavioral situations in two lines of mice, BR and BS, previously selected for their sensitivity to an anxiogenic benzodiazepine (BZ) receptor inverse agonist, Methyl beta-carboline-3-carboxylate (beta-CCM). BR is highly resistant, and BS, highly sensitive to beta-CCM-induced seizures. Tests used included an assessment of general locomotor activity, several situations classically used for measuring fear-motivated behaviors (open field, thigmotaxis, elevated plus-maze, light-dark discrimination, staircase), a test for measuring exploration (holeboard), and a test for measuring nociception (hot-plate).

Long lasting increase in nociceptive threshold induced in mice by forced swimming: involvement of an endorphinergic mechanism.

Mice submitted to forced swimming session(s) displayed a long lasting modification in their nociceptive threshold, assessed through their jump latency from a hot plate (55 degrees C). Thus two forced swimming sessions (6 min each, 8h apart), in water at 33 degrees C, increased by about 50% the jump latency when the hot plate test was performed 14 hours, 3 days or 6 days thereafter. The water temperature (16 degrees C vs 33 degrees C) had no critical influence in this respect.

Comparison of behavioural effects of NocII or NocIII, two related pronociceptin-derived peptides.

Prepronociceptin contains, in addition to nociceptin, other potentially excisable peptides which may have physiological significance. We have here considered NocII, a heptadecapeptide whose sequence lies immediately downstream of that of nociceptin in the precursor polypeptide, as well as NocIII which corresponds to NocII extended by a stretch of three arginine residues. When i.

The proenkephalin A-processing product peptide E, which encompasses two enkephalin sequences, has a much lower opioid activity than beta-endorphin.

Peptide E is a 25-amino acid peptide derived from proenkephalin A that was originally isolated from the bovine adrenal medulla. Bovine peptide E (BPE), which possesses a Met- and a Leu-enkephalin sequence at its N- and C-terminus, respectively, has been described as a highly potent and selective mu-opioid receptor agonist. Paradoxically, the frog counterpart of peptide E (FPE), which exhibits only two amino acid substitutions (Met15-->Gln and Leu25-->Met) compared with BPE, was found to be totally devoid of antinociceptive activity.

[Cloning of prepronociceptin has led to the discovery of other biologically active peptides].

Among the opioid receptors family, the cloning of the mu, kappa and delta receptors was followed by that of another member, named ORL1 (Opiate Receptor Like 1). In spite of obvious homologies with the mu, kappa and delta receptors, ORL1 does not display a relevant affinity for the endogenous ligands of these former receptors (beta endorphin, enkephalins, dynorphin A..

Nociceptin-induced apparent hyperalgesia in mice as a result of the prevention of opioid autoanalgesic mechanisms triggered by the stress of an intracerebroventricular injection.

The effects on nociperception of nociceptin/Orphanin FQ (noc/OFQ), the endogenous ligand of the ORL1 (opioid receptor like 1) receptor, have been evaluated in mice upon intracerebroventricular injection of 10 to 10,000 ng doses of the peptide. In the hot plate test (55 degrees C) the licking, rearing and jump latencies were significantly reduced by noc/OFQ (100-250 ng). Noc/OFQ (100-1000 ng) also reduced the latency to tail withdrawal in the tail flick test.

Mechanism of the hypothermic effect of MPP+ administered centrally in mice.

The neurotoxin methyl phenyl pyridinium (MPP+) was administered intracerebroventricularly (i.c.v.

Orphan neuropeptide NocII, a putative pronociceptin maturation product, stimulates locomotion in mice.

NocII is a heptadecapeptide whose sequence lies immediately downstream of nociceptin, the newly discovered natural agonist of the ORL1 receptor, in pronociceptin, nociceptin's precursor polypeptide. Since the sequence of NocII is framed by putative convertase excision sites and it totally conserved across murine and human species, we have sought to determine whether this orphan neuropeptide might by physiologically significant, i.e.

Nociceptin stimulates locomotion and exploratory behaviour in mice.

The recently characterized heptadecapeptide nociceptin, the endogenous agonist of the orphan opioid receptor-like 1 (ORL1 receptor), has been tested for its effects on locomotion and exploratory behaviour in mice. I.c.

A proenkephalin A-derived peptide analogous to bovine adrenal peptide E from frog brain: purification, synthesis, and behavioral effects.

A peptide derived from the posttranslational processing of proenkephalin A was isolated from an extract of the brain of the European green frog Rana ridibunda and its primary structure established as: Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-Gly-Arg10- Pro-Glu-Trp-Trp-Gln-Asp-Tyr-Gln-Lys-Arg20-Tyr-Gly-Gly-Phe-Met. The structure was confirmed by chemical synthesis. The peptide represents an amphibian equivalent of bovine adrenal peptide E [preproenkephalin A (206-230)-peptide] but the sequence contains two amino acid substitutions (Met15-->Gln and Leu25-->Met) compared with the mammalian peptide.

Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor.

The ORL1 receptor, an orphan receptor whose human and murine complementary DNAs have recently been characterized, structurally resembles opioid receptors and is negatively coupled with adenylate cyclase. ORL1 transcripts are particularly abundant in the central nervous system. Here we report the isolation, on the basis of its ability to inhibit the cyclase in a stable recombinant CHO(ORL1+) cell line, of a neuropeptide that resembles dynorphin A9 and whose amino acid sequence is Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln.

Extensive brain mapping of calcitonin-induced anorexia.

The purpose of this study was to compare the localization in the brain of calcitonin-induced anorexia to the distribution of calcitonin binding sites (as described by others). We, thus, performed an extensive mapping of brain structures to determine those involved in calcitonin-induced anorexia. A significant anorexia is found after injection of calcitonin (15 ng in 0.

Analgesic effect of the direct D2 dopamine receptor agonist RU 24926 and cross tolerance with morphine.

The direct D2 dopamine receptor agonist RU 24926, administered subcutaneously to mice, elicited, starting at the dose of 0.125 mg/kg, a dose dependent analgesic effect, assessed as the jump latency from a hot plate (55 degrees C). The analgesic effect induced by 0.

Rapid and long lasting reduction of the hypothermic effect of a D2 dopamine agonist after an intracerebroventricular injection of 6-hydroxydopamine.

In mice pretreated intracerebroventricularly (i.c.v.

Tolerance to the hypothermic but not to the analgesic effect of [D-Trp11]neurotensin during the semichronic intracerebroventricular infusion of the peptide in rats.

The peptidase-resistant derivative of neurotensin, [D-Trp11]neurotensin, has been continuously infused intracerebroventricularly (75 ng/h) with an osmotic minipump for 10 days. On several days during this infusion the locomotor activity, the body temperature, the food intake, the body weight, and the nociceptive response in the plantar test were measured. A nonsignificant decrease of body temperature and a sustained analgesic effect were observed at each time considered.

Analgesic effects of antibiotics in rats.

Studies in forelimb-deafferented rats suggest that treatment with certain antibiotics can decrease pain sensation. To test this hypothesis, the analgesic effects of nine randomly selected antibiotics were studied in rats by using a constant-temperature hotplate. The results show that several antibiotics have antinociceptive properties, and two of them, chloramphenicol and ampicillin, can produce analgesia in a dose range used in human therapy (100 mg/kg).

[Hypoalgesia in partially de-afferented rats].

When placed on a hot plate, rats with 5 consecutive dorsal root sections, present long licking-latencies of the posterior limbs, sign of a generalised hypoalgesia. To determine if this hypoalgesia is the result of the deafferentation or of the extent of the anterior limb automutilation performed by such deafferented rats, the licking-latency was measured in two groups of deafferented rats. In one of these groups all the rats performed automutilation, in the other a daily injection of amoxicillin resulted in an important reduction of the autotomic behavior.

A different balance in the sensitivity of D1 and D2 dopamine receptors accounts for differences in apomorphine-induced hypothermic effects in Swiss and C3H mice.

In several strains of mice: Swiss CD1, BALB, DBA2, C57, the mixed D1/D2 direct dopamine receptor agonist, apomorphine, elicited a marked and virtually similar hypothermic effect. By contrast, in C3H mice, this effect was obviously less and shorter. Similarly, the hypothermic effects of two direct D2 dopamine agonists RU 24926 and piribedil were respectively lesser or absent in C3H, compared to Swiss CD1 mice.

Anatomical mapping of brain sites involved in the antinociceptive effects of ketoprofen.

Ketoprofen, a non-steroidal anti-inflammatory drug, has analgesic effects in animals and humans through a peripheral as well as a central action. This study was designed to determine which brain sites are involved in the central analgesic action of ketoprofen, by using the hot-plate test. Latencies to the first hindpaw lick were recorded in animals receiving local cerebral injections of ketoprofen (10 micrograms in 0.

Antibiotics and morphinomimetic injections prevent automutilation behavior in rats after dorsal rhizotomy.

Unilateral section of dorsal roots C5 to T1 were performed in rats, and the automutilation behavior was measured by the extent of the limb lesions expressed in arbitrary units. Changes in the scores of automutilation were studied after the injection of four substances: a morphinomimetic (pethidine) and three antibiotics, chloramphenicol, amoxicillin, and doxycycline. Effects were tested on groups of at least eight rats that were compared with another group of eight animals operated on in the same way but injected with distilled water.

Anorectic effect of calcitonin, neurotensin and bombesin infused in the area of the rostral part of the nucleus of the tractus solitarius in the rat.

The three neuropeptides calcitonin, neurotensin and bombesin can decrease food intake in the rat when injected into the cerebral ventricles or into the paraventricular nucleus of the hypothalamus. The paraventricular nucleus of the hypothalamus is an important site for the integration of visceral and endocrine systems, and has connections with the nucleus of the tractus solitarius which is a major locus for visceral afferents. Since calcitonin, neurotensin and bombesin, or their receptors, have been found to be present in the nucleus of the tractus solitarius, we tested the effects of local infusions of these peptides on food intake.