The effects of intracerebroventricularly (ICV) administered secretin on the analgesic, tolerance-inducing, and dependence-inducing actions of morphine were investigated, in adult, male CFLP mice. Secretin administered doses ICV did not itself affect pain sensitivity in a heat-radiant tail flick test. However, it depressed the acute nociceptive effect of a single subcutaneous (SC) dose of morphine (4 mg/kg) after ICV (1 or 10 ng/animal) secretin administration. A dose of 10 ng secretin facilitated the development of acute morphine tolerance. On the other hand, none of the doses applied had any influence on chronic morphine tolerance, where animals were implanted SC with a morphine- containing pellet and the pain sensitivity was measured 3 days later. Morphine withdrawal signs were also evaluated by injecting naloxone. In a 100-ng dose, secretin increased the latency of the withdrawal jumping response; the peptide did not modify the other abstinence signs. These data suggest that central secretin administration can modify the analgesic effect of morphine.

Analgesics↗

PubMedDate not supplied

Inhibition of feeding by the C-terminal tetrapeptide fragment of cholecystokinin in a novel environment.

Several doses of the C-terminal tetrapeptide fragment of cholecystokinin octapeptide (CCK-5-8) were injected intraperitoneally (ip.) and intracerebroventricularly (icv.), and their effects on the feeding of 24-hr food-deprived rats in familiar and novel environments were studied. In the familiar environment, CCK-5-8 ip. or icv. had no effect on the food intake of the rats. In the novel environment (i.e. in an open field), CCK-5-8 showed merely slight effects on the main open-field parameters: only ip. administered CCK-5-8 enhanced the incidence of grooming. Of the feeding parameters tested in the open field, mainly the food intake/approach to food ratio was depressed by CCK-5-8 ip. or icv. The 24 mumole/kg ip. dose of CCK-5-8 decreased the food intake, while the 8 pmole icv. dose increased the number of approaches to food. After the treatments found to be the most effective, the latency to first bite was also enhanced. The results suggest that CCK-5-8 can amplify the arousal enhancement elicited by novelty through a central mechanism.

Animals↗

PubMedDate not supplied

Amnesic action of FMRFamide in rats.

The effects of FMRFamide on passive avoidance behaviour and electroshock-induced amnesia following intracerebroventricular administration were studied in rats. FMRFamide given immediately after the learning trial, or 20 min before the retention trial, attenuated the avoidance response, thereby impairing the consolidation and retrieval processes. Electroshock induced amnesia when applied immediately after the learning trial. Treatment with FMRFamide facilitated the amnesia of the passive avoidance response. The results indicate that FMRFamide peptide belongs in the class of neuropeptide which are amnesic.

Amnesia↗

PubMedDate not supplied

Phe-Met-Arg-Phe-amide (FMRFamide) stimulated growth hormone secretion in conscious OVX rats.

The presence of FMRFamide (Phe-Met-Arg-Phe-amide)-like immunoreactivity in neuronal elements in the hypothalamus suggested a role for this in the hypothalamic control of the anterior pituitary function. We report here the action of FMRFamide on growth hormone release following intracerebroventricular administration to rats. The injection of 200 ng (313.8 picomoles) of FMRFamide (in 2 ul) produced a significantly increased plasma GH 15 min after injection. The GH-increasing effect of 400-800 ng (627-1255 picomoles) of FMRFamide was already developed after 5 min and lasted up to 30 min. No change was detected in the plasma FSH, LH and prolactin levels at any time during the experimental period. The intravenous administration of 10, 30 or 100 ug of FMRFamide had no effect on the plasma GH level. We conclude that FMRFamide can act at low doses to increase GH release through the inhibition of somatostatin release or the stimulation of GRF. We could not exclude a direct site of action in the pituitaries.

Animals↗

PubMedDate not supplied

Effects of glutaurine treatment on electroshock-induced amnesia. Antiamnesic action of glutaurine.

The effects of oral glutaurine (gamma-L-glutamyl-taurine, LitoralonR Chinoin, Budapest) treatment on electroconvulsive shock-induced amnesia were studied. Oral treatment with glutaurine in a dose of 1-20 micrograms was ineffective on electroshock-induced amnesia if the treatment was applied before the electroconvulsive shock. Fifty micrograms given in the same experimental paradigm could attenuate the amnesia considerably. When the treatment with glutaurine was applied immediately after the electroconvulsive shock, even 1 and 10 micrograms doses were effective in attenuating the amnesia in both the 24h and 48h retestings. However when glutaurine was given one hour before the 24h and 48h retestings, it proved to be ineffective. The data indicate that glutaurine is able to prevent electroconvulsive shock-induced amnesia by counteracting the effect of the electroconvulsive shock on the memory consolidation phase, but it is less effective on learning or it is ineffective on retrieval processes.

Amnesia↗

PubMedDate not supplied

Influence of dipeptides on precipitated morphine withdrawal in the mouse.

Effects of various dipeptides on naloxone-precipitated morphine withdrawal were studied in the mouse. Mice were rendered dependent on morphine by implantation of morphine pellets and the withdrawal syndrome was measured by the latency of the onset of stereotyped jumpings. In accordance with previous data, subcutaneous injection of Z-prolyl-D-leucine significantly delayed the onset of morphine withdrawal. The all-L enantiomer of the dipeptide (Z-L-prolyl-L-leucine) did not affect morphine withdrawal in the dose studied. Replacement of L-proline by L-glutamate or L-pyroglutamate (Z-L-glutamyl-L-leucine and L-pyroglutamyl-L-leucine) resulted in dipeptides which were more potent towards morphine withdrawal than Z-prolyl-D-leucine. Z-L-glycyl-L-proline attenuated the morphine withdrawal syndrome more effectively than Z-L-prolyl-D-leucine, but Z-L-leucyl-L-glycine was ineffective in this respect. The data reveal that certain dipeptides--which in their nonprotected forms are normal sequences of endogenous peptides--affect morphine withdrawal more potently than Z-prolyl-D-leucine, a synthetic dipeptide known to attenuate morphine dependence.

Animals↗

PubMedDate not supplied

Intracerebroventricular somatostatin attenuates electroconvulsive shock-induced amnesia in rats.

In the present study the effect of intracerebroventricularly (ICV) administered somatostatin on electroconvulsive shock-(ECS) induced retrograde amnesia was investigated in rats. The ECS significantly decreased foot shock-induced avoidance latency. Somatostatin in a dose of 1 microgram/4 microliter (ICV) had no action on the ECS-induced retrograde amnesia, while in a dose of 4 micrograms/4 microliters it significantly increased the avoidance latency if the treatment was performed immediately, 4 hr, 20 hr or 23 hr after the ECS. The results suggest that ICV administered somatostatin has an antiamnesic effect.

Amnesia↗

PubMedDate not supplied

Multiple treatment potentiates the anticonvulsive activity of cholecystokinin octapeptides.

The dose-response curves for the anticonvulsive activity of sulfated and nonsulfated cholecystokinin octapeptide (CCK-8-SE and CCK-8-NS) against picrotoxin-induced (6 mg/kg SC) seizures were assessed either following or without pretreatment with a single high dose of CCK-8-SE or CCK-8-NS, to examine acute tolerance to the effect after IP injections in mice. As CCK-8-SE or CCK-8-NS pretreatment, a 1.6 mumole/kg dose was injected 2 hr prior to the second injection. No acute tolerance to the anticonvulsive activity was demonstrated, and CCK-8-NS pretreatment significantly potentiated its own anticonvulsive activity. Chronic (8-day) daily treatment with a 0.16 mumole/kg dose of CCK-8-SE or CCK-8-NS antagonized seizures by picrotoxin, presumably in a cumulative manner. To investigate the interactions of CCK octapeptides with other anticonvulsive agents, picrotoxin-induced seizures were antagonized with several doses of diazepam following or without acute, high-dose pretreatment with CCK-8-SE or CCK-8-NS. The two octapeptides only slightly modified the activity of diazepam: CCK-8-SE pretreatment displayed a tendency to antagonize it, while CCK-8-NS pretreatment to potentiate it. The results suggest that multiple treatment with CCK-8 induces sensitization of CCK receptors mediating anticonvulsive activity.

Animals↗

PubMedDate not supplied

Opposite effects of intraventricular and intracisternal administration of vasopressin on blood pressure in rats.

Lysine-8-vasopressin (LVP) was injected into the lateral ventricle (ICV) or into the cisterna magna (c.m.) of ether-anesthetized rats. ICV injection of LVP decreased the blood pressure (BP), whereas c.m. administration increased it. The opposite effects of ICV versus c.m. administration of the peptide might be related to differences in brainstem versus limbic-midbrain structures in the regulation of blood pressure, and suggest that both mechanisms can be influenced by vasopressin.

Animals↗

PubMedDate not supplied

The effect of beta-(Tyr9)melanotropin-(9-18) on active avoidance behavior, electroconvulsive shock-induced amnesia and T-discrimination learning of rats.

The effect of beta-(Tyr9)melanotropin-(9-18) was investigated on active avoidance behavior, electroconvulsive shock (ECS)-induced amnesia and T-discrimination learning in rats. The decapeptide inhibited the extinction of active avoidance behavior. It was also able to block ECS-induced amnesia if the treatment was performed immediately, or 4 hr or 20 hr after the ECS. In the T-discrimination paradigm the peptide facilitated spatial discrimination learning and reversal learning. These results suggest that beta-(Tyr9)melanotropin-(9-18) can influence learning and memory processes in different behavioral tests.

Amnesia↗

PubMedDate not supplied

Intracerebroventricularly administered atrial natriuretric peptide (ANP) antiserum attenuates fear-motivated learning behavior in rats.

Previous studies have demonstrated that rANP(1-28) administered into the lateral cerebroventricle facilitates consolidation of the passive avoidance response and delays extinction of the active avoidance response in fear-motivated learning in rats. To study the role of endogenous ANP in the same learning processes, the effects of different dilutions of ANP antiserum were investigated following their intracerebroventricular administration to rats. At dilutions of 1:40 and 1:60, the ANP antiserum attenuated consolidation of the passive avoidance response. It also facilitated extinction of the active avoidance response at a dilution of 1:2. The results suggest that endogenous ANP might be considered a modulating agent in the brain, and is involved in the learning processes and memory trace formation, since intracerebroventricularly administered antiserum against ANP attenuated fear-motivated learning behavior in the experimental animals.

Animals↗

PubMedDate not supplied

The effects of neurohypophyseal hormones on tolerance to the hypothermic effect of ethanol.

Mice were made tolerant to the hypothermic effect of ethanol by repeated administration of ethanol (4 g/kg, 25% v/v, IP) on three consecutive days. The colonic temperature was measured in individually-housed animals immediately before and 45 min after ethanol treatment. Peptide treatments with various schedules were made SC 2 hr before the first ethanol challenge. The decrease in hypothermic response was accepted as a tolerance phenomenon, which developed in control animals by day 2. A single injection of oxytocin (OXT) or lysine vasopressin (LVP [0.1 or 1 IU peptide] animal) before the first ethanol injection did not change the initial sensitivity to ethanol. This absence of acute interactions is also reflected in the sleep onset and sleep duration after 5 g/kg ethanol (IP). In contrast, both OXT and LVP affected the development of tolerance. Repeated treatments with graded doses of OXT (0.5-2 IU) or LVP (0.25-1 IU) every day for 3 days blocked the development of tolerance. 0.002 IU LVP facilitated the development of hypothermic tolerance. The remaining doses of the peptides were ineffective. A high dose of LVP (1 IU) facilitated hypothermic tolerance if the peptide was injected when tolerance to ethanol had developed fully without previous peptide treatment. OXT, on the other hand, was ineffective in this particular experimental model. The data suggest that both neurohypophyseal hormones (LVP and OXT) block the early developmental phase of tolerance to ethanol. On the other hand, LVP facilitated the expression of tolerance if the peptide was given to mice with fully developed tolerance.

Animals↗