Rosanna Poggioli

ACTH-(1–24) and α-MSH antagonize feeding behavior stimulated by kappa opiate agonists

Abstract ACTH-(1–24) and α-MSH, intracerebroventricularly (ICV) injected at the doses of 4 and 10 μg/animal, respectively, markedly inhibited spontaneous feeding in adult Sprague-Dawley rats, the effect remaining significant for 6–9 hours. At these same doses, ACTH-(1–24) and α-MSH abolished the feeding-stimulatory effect of the kappa opiate receptor agonist pentazocine, intraperitoneally (IP) injected at the dose of 10 mg/kg. The same antagonism was obtained by ICV injection of ACTH-(1–24) into rats IP treated with two other kappa opiate agonists, bremazocine and tifluadom, at the doses of 1 and 5 mg/kg, respectively. These data suggest that melanocortin peptides play an inhibitory role in the complex regulation of food intake, and further support and extend the hypothesis of a melanocortin-opioid homeostatic system, its two neuropeptide components usually having opposite, mutually-balancing effects.

Polymodal dose-response curve for oxytocin in the social recognition test

Available data concerning the effect of oxytocin on memory are often inconsistent. In the present study it was found that oxytocin, intracerebroventricularly injected to adult male rats in a dose range of 1 fg-10 ng/rat immediately after a 5-minute encounter with a juvenile, significantly reduces the social investigation time of the adult rat towards the same juvenile during a second encounter (120 min later) with two peaks of activity, at 10 fg and 1 ng/rat. Larger doses of oxytocin were ineffective. The oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin, injected 5 min before oxytocin by the same route and at the same doses, while being ineffective per se, completely abolished the memory-improving effect of a low dose of oxytocin (1 ng/rat) and, on the other hand, turned into memory-improving the effect of a high dose of oxytocin (500 ng/rat).

Nitric oxide is involved in male sexual behavior of rats

In male rats, whether sexually experienced or sexually naive, the intraperitoneal administration of L-arginine (the natural substrate for nitric oxide synthase) (10, 25, 50 mg/kg) both increased the percentage of copulating in sexually naive rats and improved the indexes of sexual performance in sexually experienced rats, whereas the intraperitoneal administration of N(G)-nitro-L-arginine methyl ester (L-NAME) (a potent inhibitor of nitric oxide synthase) (10, 25, 50 mg/kg) had opposite effects. In contrast, after intracerebroventricular administration, L-arginine (25, 50, 100 microg/rat) had no effect - whether in naive or in experienced rats - whereas L-NAME completely prevented ejaculation in naive rats, at the dose of 100 microg/rat, but had no effect at all in experienced rats, up to the dose of 300 microg/rat. Finally, a direct relationship seems to exist between male copulatory performance and nitric oxide synthase activity in a discrete and defined brain area, the paraventricular nucleus of the hypothalamus: indeed, nitric oxide synthase mRNA expression in this nucleus in sexually potent rats is about twice that in sexually impotent rats. It is concluded that nitric oxide synthase is involved in the expression of male sexual activity, in spite of some inconsistencies that are hard to interpret.

Corticotropin inhibits food intake in rats

The synthetic corticotropin ACTH (1-24) (tetracosactide), injected into a brain lateral ventricle after a 24h starvation period or into the ventromedial hypothalamus during the nocturnal feeding phase, markedly inhibited food intake, in rats. In starved rats, the dose of 4 micrograms/rat was maximally effective and reduced food intake by 76.6% during the first hour after treatment. The same dose, injected into the ventromedial hypothalamus, significantly inhibited food intake also in normally fed rats during the nocturnal phase (58.6% reduction during the 90 minutes of observation). These findings suggest that corticotropin may play a role in the central control of appetite.

Antidepressants and opiates interactions: pharmacological and biochemical evidences.

Imipramine, chronically administered to rats (20 mg/Kg/day X 20) has a potent analgesic effect per se (hot plate test), increases morphine analgesia and intensifies morphine withdrawal syndrome precipitated by naloxone. Receptor binding studies performed with 3H-naloxone revealed that chronic administration of imipramine results in a marked increase of opiate binding sites in the brain. This increase persisted when the rats treated chronically with imipramine were rendered tolerant to morphine by s.c. implantation for 3 days of a pellet containing 100 mg of morphine. Since antidepressants exert their own analgesic effect, increase morphine analgesia and displace opiate receptor binding, it may be that by interacting with the opiate receptor complex imipramine induces supersensitivity in opiate recognition binding sites.

Inhibition of feeding by ACTH-(1-24): behavioral and pharmacological aspects

The time course of the behavior of rats fasted for 24 h was analyzed with observation starting either 10 or 60 min after the i.c.v. administration of ACTH-(1-24) (4 micrograms/animal). The anorectic effect of this peptide was direct and specific because it could be dissociated in time from the grooming-inducing effect. The effect is a central one, not linked either to an interaction with the peripheral feeding-regulatory system, or to the release of adrenal steroids. ACTH-(1-24), like corticotropin-releasing factor (CRF), is capable of antagonizing the stimulation of feeding seen during starvation, insulin (10 IU/kg s.c.)-induced hypoglycemia, stimulation of GABAergic (muscimol, 250 ng/rat i.c.v.), noradrenergic (norepinephrine, 20 micrograms/rat i.c.v.) or opioidergic systems. The data suggest that both CRF and ACTH may be considered as putative mediators in the production of stress-induced anorexia.

Cross‐Species Comparison of the ACTH‐induced Behavioral Syndrome

Most of the dogs given ACTH intracisternally exhibit apparently normal behavior for about half an hour. Thereafter . . . the dogs are drowsy, yawn frequently and after about one hour they start to stretch in the way they usually do when they awake from physiological sleep. The intervals between successive stretching acts become shorter and shorter until a stretching act begins immediately after the preceding one. Despite this peculiar behavior, the dogs seem to remain in contact with the environment, as they are responsive to calls and perform normal activities without fear or aggressiveness. . . . Rabbits, cats, and rats given ACTH and MSH also exhibit stretching crises qualitatively similar to those of dogs. In rabbits and rats the stretching syndrome is preceded by increased grooming activity and scratching. Rabbits yawn more frequently than dogs. In cats, intracisternal injection of ACTH caused a marked drowsiness interrupted by stretching movements. However, doses of ACTH up to 0.02 I.U./kg injected intrarachnoidally in men caused nausea and vomiting but not stretching.

Aged rats are still responsive to the antidepressant and memory-improving effects of oxytocin

Oxytocin, intraperitoneally injected to 26-month-old male rats 60 min before testing, significantly improved social memory (at doses of 3 and 6 ng/kg) and reduced the duration of immobility in the behavioral despair test (at doses of 50 and 500 micrograms/kg). These results are in agreement with previous data obtained in adult rats and indicate that aging does not compromise the social memory improving and antidepressant-like activities of oxytocin.

Oxytocin enhances, and oxytocin antagonism decreases, sexual receptivity in intact female rats

In intact, non-ovariectomized female rats in spontaneous behavioral estrus, the i.c.v. injection of oxytocin significantly increased lordosis quotient and lordosis duration, starting from a dose of 1 ng/rat. On the other hand, the oxytocin antagonist, d(CH2)5Tyr(Me)-[Orn]8-vasotocin, injected at the same doses and by the same route, decreased lordosis quotient and lordosis duration, and prevented the effect of oxytocin. These data further support the notion that oxytocin plays a physiological role in female sexual receptivity.

Galanin inhibits sexual behavior in male rats

Intracerebroventricular injection of galanin potently inhibited (0.5 micrograms/rat) or completely suppressed (5.0 micrograms/rat) copulatory activity in sexually experienced male rats, without producing any other obvious behavioral deficit. It is suggested that galanin, known to potently stimulate feeding behavior, may be involved in the inverse modulation of feeding and sexual behaviors.