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.     

Beta-endorphin-(10-16) antagonizes behavioral responses elicited by melatonin following injection into the nucleus accumbens of rats

The behavioral changes induced by low doses of melatonin bilaterally injected into the nucleus accumbens of rats (decrease of locomotor activity and rearing and increase of grooming and sniffing behavior) were not affected by local pretreatment with beta-endorphin, but could be completely antagonized by alpha-type and gamma-type endorphins. Structure activity relationship studies revealed that the peptide beta-endorphin-(10-16) contains the essential information in this respect. The lowest effective dose of this peptide was 10 pg. The peptide, in contrast to gamma-type endorphins, did not interfere with the decrease of locomotor activity and rearing induced by injection of low doses of apomorphine into the nucleus accumbens. It is concluded that the described action of beta-endorphin-(10-16) resembles that of serotonin and various antidepressant drugs.     

Arginine vasopressin and a vasopressin antagonist peptide: Opposite effects on extinction of active avoidance in rats

Systemic injection of arginine vasopressin (AVP) (1 μ/rat) significantly prolonged extinction of a pole-jump, active avoidance response in rats; lateral ventricular injection of 1000-fold less AVP (1 ng/rat) produced similar results. A new AVP analogue, [1-deaminopenicillamine-2-(O-methyl)-tyrosine]arginine vasopressin (dPTyr-(Me)AVP), is known to antagonize behavioral and vascular effects of exogenous AVP at molar ratios of 5:1. At a dose of 100 μ/rat (subcutaneously) dPTyr-(Me)AVP produces, by itself, a behavioral effect opposite to that of exogenous AVP, namely a facilitation of extinction. Injections of dPTyr-(Me)AVP into the lateral ventricle were ineffective except at a dose of 10 μg/rat. These results confirm previous reports of the effect of vasopressin on delaying extinction of avoidance behavior, but suggest a site of action distant from the lateral ventricle.     

des-Tyr1-gamma-endorphin and haloperidol increase pineal gland melatonin levels in rats

The effect of subcutaneously injected DT gamma E (beta-endorphin, (beta E)2-17) on the pineal melatonin level was compared with that of closely related peptides and the neuroleptic drug haloperidol. As found previously, DT gamma E (3 ng/rat and 300 ng/rat) increased the melatonin levels. Similar doses of DT alpha E (beta E 2-16), DT beta E (beta E 2-31), gamma E (beta E 1-17), alpha E (beta E 1-16) and beta E 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 DT gamma E.     

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.     

gamma-Endorphin and N alpha-acetyl-gamma-endorphin interfere with distinct dopaminergic systems in the nucleus accumbens via opioid and non-opioid mechanisms

Low doses (10 ng) of the dopamine agonist apomorphine induced hypolocomotion when injected into the nucleus accumbens of rats. This behavioral response was antagonized by local treatment with either the opioid peptide gamma-endorphin (gamma E) or the non-opioid peptide N alpha-acetyl-gamma-endorphin (Ac gamma E) in a dose of 100 pg. High doses of apomorphine (10 micrograms) r amphetamine (2 micrograms) injected into the nucleus accumbens resulted in hyperlocomotion. This response was blocked by pretreatment with gamma E but not with Ac gamma E. This effect of gamma E could be prevented by local treatment with naloxone. Neither peptides interfered with the apomorphine-induced stereotyped sniffing when the substances were injected into the nucleus caudatus. It is concluded that gamma E and Ac gamma E differentially interact with distinct dopaminergic systems in the nucleus accumbens of the rat brain via an opioid and a non-opioid mechanism, suggesting that the peptide fragments originating from pro-opiomelanocortin may be specifically implicated in the control of dopaminergic activity in this brain area.