O. Gaffori

Serotonin and antidepressant drugs antagonize melatonin-induced behavioural changes after injection into the nucleus accumbens of rats

Small doses of melatonin (0.1-100 ng), injected into the nucleus accumbens of rats, decreased locomotor activity and rearing, and increased grooming and sniffing behaviour when the animals were tested in small test-cages. Larger doses of melatonin appeared to be less effective. The action of melatonin is apparently not mediated by dopaminergic systems, because the behavioural changes were not antagonized by local pretreatment with haloperidol or sulpiride. Injection of serotonin antagonists (methysergide and cyproheptadine) into the nucleus accumbens resulted in similar behavioural changes as was found after treatment with melatonin. Treatment with serotonin and various antidepressant drugs (zimelidine, mianserin, nortriptyline, clomipramine, desipramine) injected into the nucleus accumbens, completely inhibited the melatonin-induced behavioural responses. The antidepressants did not significantly interfere with the decrease of locomotor activity and rearing induced by injection of small doses of the dopamine agonist, apomorphine, into the nucleus accumbens. These results suggest that there is an interrelationship between melatonin and serotonin systems in the nucleus accumbens and showed that various antidepressant drugs, similar to serotonin, antagonized the behavioural effects of melatonin after injection into the nucleus accumbens.

Differential responses in immunoreactive arginine-vasopressin content of microdissected brain regions during passive avoidance behavior

Immunoreactive arginine-vasopressin (IR-AVP) was measured in various hypothalamic and extrahypothalamic nuclei of male Wistar rats immediately after the 24 h retention test of a passive avoidance response. IR-AVP concentrations in paraventricular, suprachiasmatic and lateral septal nuclei were significantly decreased in comparison with the non-shocked rats, while IR-AVP was increased in the central amygdala nucleus, subfornical organ and locus coeruleus. No significant differences in IR-AVP levels were found in the habenular and periventricular hypothalamic nucleus, organum vasculosum of lamina terminalis and medial and dorsal raphe nucleus.

Arginine-vasopressin content of hippocampus and amygdala during passive avoidance behavior in rats

Arginine-vasopressin (AVP) is involved in memory processes. The memory effects of AVP are mediated by neuronal mechanisms taking place in limbic-midbrain structures. Therefore, immunoreactive AVP (IR-AVP) was measured in hippocampus and amygdala of male Wistar rats during acquisition and retention of passive avoidance behavior. IR-AVP concentration was decreased in the hippocampus immediately after the learning trial while IR-AVP content of the amygdala was not affected. Animals that showed the passive avoidance response (good avoiders) at the 24 h or 120 h retention test had a reduced IR-AVP concentration in the hippocampus immediately after the test. However, IR-AVP content of the hippocampus was not different from that of non-shocked control animals when measured immediately before the 120 h retention test. Poor avoiders that showed only minor avoidance behavior did not differ in hippocampal IR-AVP content from non-shocked control animals. IR-AVP content of the amygdala was also not altered after the retention session. These effects on IR-AVP content could only be shown in animals that were trained and habituated to the passive avoidance procedure. Such trained and habituated animals had an IR-AVP level in the hippocampus which did not differ from that of animals that were left undisturbed until sacrifice. When the animals were not trained, but placed for the first time in the passive avoidance apparatus without being exposed to the learning trial, the hippocampal IR-AVP content was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of substance P and fragments on passive avoidance behavior.

N-terminal and C-terminal fragments of substance P (SP) have been shown to exert opposite effects on antinociception, grooming and fighting in mice. The present experiments explored whether these findings could be generalized to passive avoidance behavior. Substance P (SP-(1-11)) and the c-terminal, fragment pyroglutamyl-SP-(7-11) attenuated passive avoidance behavior when picogram amounts were injected into the nucleus accumbens. In contrast, the N-terminal fragment, SP-(1-7) had an opposite effect and facilitated passive avoidance behavior.

Time-related memory effects of vasopressin analogues in rats

The present study was designed to investigate critical time periods for the memory modulating effect of vasopressin and several analogues in rats using a passive avoidance test as the behavioral paradigm. AVP, AVP-(4-8) and AVP-(5-8) were more effective when given immediately after the learning trial (consolidation), while AVP-(1-8) (DGAVP) and AVP-(5-9) were more active when administered one hour prior to the retention test (retrieval). DDAVP and AVP-(4-9) were highly active both when given immediately after the learning trial or 1 hour before the retention test. The period between 12 and 18 hr after the learning trial appeared to be another sensitive period. Administration, in particular of DGAVP, and AVP-(5-9) at 12, 15, and 18 hr after the learning trial induced marked retention of the avoidance response at the 24 hr retention test. Injection at 6 and 21 hr after the learning trial was the least effective in facilitating passive avoidance latencies. The more stable analogue DDAVP facilitated avoidance latencies irrespective of the time of administration. Vasopressin and related peptides exert a long term effect on avoidance behavior. However, DGAVP and AVP-(5-9) facilitated passive avoidance behavior at the 24, 48, and 72 hr retention test if administered immediately after the learning trial. If injection was postponed till 15 hr after the learning trial, passive avoidance behavior was facilitated at the 24 hr retention test only.(ABSTRACT TRUNCATED AT 250 WORDS)

Levels of arginine-vasopressin in cerebrospinal fluid during passive avoidance behavior in rats.

The concentration of immunoreactive arginine-vasopressin (IR-AVP) was measured in the cerebrospinal fluid (CSF) during acquisition and retention of passive avoidance behavior. IR-AVP level in CSF of male Wistar rats immediately after the learning trial was increased; the rate of which was related to the intensity of the electric footshock during the learning trial and the avoidance latency as measured 1 day after the learning trial. Immediately after the 24 h retention test IR-AVP levels were significantly increased in rats subjected to the low (0.25 mA) shock intensity during the learning trial, but IR-AVP levels of rats exposed to the high shock (1.0 mA) were under the limit of detection. If the retention test was postponed till 5 days after the learning trial, the increase of IR-AVP level in the CSF was related to avoidance latencies which reflect the intensity of aversive stimulation (electric footshock). The results suggest an association between central AVP release and passive avoidance behavior and may be indicative of the role of this peptide in neuronal mechanisms underlying learning and memory processes.

Effect of des-Tyr1-[gamma]-endorphin and des-enkephalin-[gamma]-endorphin on active and passive avoidance behavior of rats; A dose-response relationship study

The potency of two beta-endorphin fragments, des-Tyr1-gamma-endorphin (DT gamma E, beta E-(2-17) and des-enkephalin-gamma-endorphin (DE gamma E-(6-17) was compared on extinction of pole-jumping avoidance behavior and on retention of a one-trial step-through passive avoidance procedure. Both peptides facilitated the extinction of pole-jumping avoidance behavior and attenuated passive avoidance behavior. The gamma-type endorphin exhibited an inverted U-shaped dose-response curve on passive avoidance behavior but not on extinction of pole-jumping avoidance behavior. DE gamma E appeared to be approximately three times more potent than DT gamma E on extinction of pole-jumping avoidance behavior but one hundred times more potent on passive avoidance behavior. It is suggested that DE gamma E rather than DT gamma E represents the endogenous neuroleptic-like neuropeptide derived from beta-endorphin.

des-Tyr1-γ-Endorphin and haloperidol increase pineal gland melatonin levels in rats ☆

Abstract The effect of subcutaneously injected DTγE (β-endorphin, (βE)2–17) on the pineal melatonin level was compared with that of closely related peptides and the neuroleptic drug haloperidol. As found previously, DTγE (3 ng/rat and 300 ng/rat) increased the melatonin levels. Similar doses of DTαE (βE 2–16), DTβE (βE 2–31), γE (βE 1–17), αE (βE 1–16) and βE failed to significantly change the melatonin levels in both the dark and the light phase. Haloperidol in a dose of 300 ng/rat exhibited a similar effect as DTγE.

N[alpha]-acetyl-[gamma]-endorphin is an endogenous non-opioid neuropeptide with biological activity

N alpha-acetyl-gamma-endorphin (Ac gamma E) was identified in the rat neurointermediate pituitary, based on its immunological properties, comigration with synthetic Ac gamma E on HPLC and resistance to aminopeptidase-M degradation. The peptide appeared to be the main form of gamma-endorphin (gamma E) in this tissue and in brain areas remote from the hypothalamus (hippocampus, septum, amygdala). The anterior pituitary, the hypothalamus and the thalamus contained almost exclusively the non-acetylated form of gamma E. In contrast to gamma E, Ac gamma E was completely devoid of specific affinity for brain opiate binding sites. Yet, the peptide mimicked gamma E in that it potently attenuated passive avoidance behaviour in rats, when injected topically into the nucleus accumbens. It is concluded that Ac gamma E is an endogenous neuropeptide with non-opioid biological activity. N alpha-acetylation may not merely represent a mechanism for the inactivation of opioid activities of endorphins, but rather allow the organism to select specific sets of biological activities that reside in the endorphin structure.

Bimodal effect of oxytocin on avoidance behavior may be caused by the presence of two peptide sequences with opposite action in the same molecule

Oxytocin (OXT) reduced locomotion, rearing, grooming and bolus production in a circular open field at 15 min, but not at 60 min, after a subcutaneous (s.c.) injection. The OXT fragments OXT-(1-8), OXT-(4-9), OXT-(4-8), OXT-(5-9) and OXT-(5-8) had no effect at 15 min or 60 min after s.c. injection. OXT and its fragments attenuated passive avoidance behavior following postlearning (consolidation test) or preretention (retrieval test) injection. Some of the fragments were more potent than the parent molecule. The extinction of pole-jumping avoidance behavior was inhibited by OXT-(1-9) in doses of 1 and 3 micrograms s.c. Doses lower than 1 microgram had no effect or even tended to facilitate extinction. This bimodal effect was more pronounced when OXT fragments OXT-(4-9) and OXT-(5-9) were used. S.c. injection of these peptides in low doses (0.01-0.001 microgram) caused facilitation, and in doses higher than 0.1 microgram inhibition, of pole-jumping avoidance behavior. Removal of the Gly9-NH2 moiety eliminated the bimodal effect; such peptides (OXT-(1-8), OXT-(4-8), OXT-(5-8) caused facilitation of extinction only. Since the C-terminal peptides Pro-Leu-Gly-NH2 and Leu-Gly-NH2 both seem to inhibit extinction of pole-jumping avoidance behavior, it is possible that there are two sequences in the OXT molecule, which act in opposite ways.