T.B. van Wimersma Greidanus

Vasopressin and Memory Consolidation

Publisher Summary The hypothalamic-neurohypophyseal system possibly makes use of (a) the general circulation for peripheral effects of posterior pituitary hormones; (b) the portal vessel system for the regulation of anterior pituitary function; and (c) the cerebrospinal fluid for CNS activities. Evidence is presented in the chapter that vasopressin and its analogues facilitate the consolidation of learned behavior patterns. Under certain conditions, these peptides facilitate the acquisition of active avoidance behavior and increase the resistance to the extinction of active and passive avoidance behavior and of sexually motivated approach behavior as well. Intraventricular administration of minute amounts of vasopressin analogues facilitates memory consolidation. This supports the idea that the behavioral effect of these polypeptides is centrally mediated. Vasopressin antibodies, which are assumed to neutralize in situ vasopressin released into the cerebrospinal fluid (CSF), prevent memory consolidation. Studies on paradoxical sleep in diabetes insipidus rats reveal disturbances in hippocampal theta frequencies and strengthen the hypothesis that memory consolidation is under the influence of vasopressin analogues. The development of resistance to the analgesic action of narcotic analgesics is facilitated by the administration of vasopressin analogues and markedly retarded in diabetes insipidus rats. These and other results suggest that the memory consolidating effects of vasopressin analogues are of a more general nature.

Barrel rotation induced by vasopressin and related peptides in rats.

Intraventricular injection of arginine-8-vasopressin and its analogues vasotocin and lysine-8-vasopressin into rat brain evoked a special rotational behavior resembling somatostatin-induced barrel rotation [1]. Oxytocin and oxypressin were less active while vasopressin fragments had no effect. Vasopressin-induced barrel rotation was accompanied by pathological symptoms indicating a disturbance of muscle tone regulation and is considered to be a non-specific and toxic effect. This rotational behavior was not prevented by atropine, propranolol, phentolamine, methylsergide or haloperidol but was reduced by chlorpromazine, probably due to the latters muscle relaxing activity.

Effects of hypophysectomy and ACTH1–10 on responsiveness to electric shock in rats

Response behavior of rats to unescapable electric shock was studied in intact and hypophysectomized animals. The threshold for flinch, jerk, run and jump was significantly lowered in hypophysectomized rats as compared to that of intact controls. Treatment with the ACTH analogue ACTH1–10 did not affect threshold levels in hypophysectomized nor in intact rats. It is concluded that the stimulating effect of ACTH1–10 on conditioned avoidance acquisition in hypophysectomized rats is not caused by an influence on sensory capacities.

The Hypothalamo-Neurohypophyseal System and the Preservation of Conditioned Avoidance Behavior in Rats

Publisher Summary This chapter focuses on the hypothalamo-neurohypophyseal system and the preservation of conditioned avoidance behavior in rats. Removal of the posterior lobe of the pituitary in rats results in a disturbance of the release of adrenocorticotropic hormone (ACTH) in response to neurogenic and emotional stress, while that to somatic or systemic stress remains unaltered. Posterior lobectomized rats subjected to transfer into a strange environment, to sound or to pain respond significantly less to these stresses with their plasma corticosterone levels than sham-operated control animals. The mode of action of lysine vasopressin (LVP) and analogs is unknown. The long term effect of these peptides suggests that rather permanent changes take place that facilitate the consolidation of aversively motivated behavior, presumably by changing the properties of neuronal and synaptic membranes. It was found that desglycinamide lysine vasopressin (DG-LVP) prevented puromycin-induced memory-blockade in mice. In conclusion, the posterior pituitary and LVP profoundly affect acquisition and maintenance of aversely motivated active and passive avoidance behavior.

Comparison between excessive grooming induced by bombesin or by ACTH: the differential elements of grooming and development of tolerance

Bombesin and ACTH-(1-24) induce a dose dependent increase in grooming behavior. Lower doses of bombesin induce a more general type of compulsive grooming in which most elements are involved, whereas higher amounts of bombesin induce a shift towards the element scratching at the cost of bodily grooming and sexual grooming. In contrast ACTH-(1-24) induces a dose dependent increase of all elements of grooming. It is concluded that the grooming displayed by animals treated with ACTH-(1-24) or with bombesin is of a completely different nature. In addition it is observed that under the conditions used tolerance occurs for the grooming inducing effect of ACTH-(1-24), but not for that of bombesin. Moreover, it appears that no cross tolerance exists between bombesin and ACTH-(1-24).

Plasma and cerebrospinal fluid α-MSH levels in the rat after hypophysectomy and stimulation of pituitary α-MSH secretion

Immunoreactive α-MSH was measured in cerebrospinal fluid (CSF) and plasma of rats. While treatment with haloperidol increased α-MSH levels in the plasma concentration of α-MSH in the CSF showed little change. Hypophysectomy also had little effect on the concentration of α-MSH in the CSF despite the fall in plasma α-MSH levels. This lack of correlation between α-MSH levels in the CSF and plasma suggests that the systemic circulation does not deliver α-MSH to the CSF. The apparently normal levels of α-MSH in the hypothalamus after hypophysectomy suggests that this tissue is able to synthesize α-MSH and it is possible that the hypothalamus is a source of the α-MSH in the CSF.

Effect of methadone on plasma arginine vasopressin level and urine production in conscious dogs.

The aim of this study was to examine the effect of i.v. methadone on the plasma arginine-vasopressin (AVP) levels and urine production in 9 conscious dogs. A highly significant increase from the baseline plasma AVP values of below 3 pg/ml occurred within 5 min following methadone administration. Maximum levels were reached within 30-50 min post-injection and varied from 18.5 to 100 pg/ml. A significant decrease in urine production was not seen under these experimental conditions. Mean arterial blood pressure did not change significantly during the experiment. Apart from the partial influence of the methadone-induced respiratory acidosis, we postulate a direct relationship between i.v. administration of methadone and the increased plasma AVP levels in dogs.

Excessive grooming induced by somatostatin or its analog SMS 201-995

Intracerebroventricular (i.c.v.) administration of somatostatin or SMS 201-995 induces excessive grooming behavior in rats. The grooming inducing effect of somatostatin is rather weak, as doses of 300 ng or less did not result in increased total grooming scores. In contrast a dose of 10 ng SMS 201-995 already significantly increased the total grooming scores. However, doses of 100 ng and more did not further increase the total grooming scores reached with a 50 ng dose of this peptide. Systemic administration of SMS 201-995 in doses up to 900 micrograms did not result in excessive grooming behavior. The patterns of excessive grooming induced by i.c.v. SMS 201-995 and somatostatin were characterized by a predominant display of scratching. Since peptide-induced scratching is mainly due to activation of opiate receptor systems it is suggested that opiate receptors are involved in the behavioral response to SMS 201-995 and somatostatin administration. This suggestion is further supported by the suppressive effect of naloxone on excessive grooming induced by these peptides. Haloperidol and neurotensin also suppress the excessive grooming induced by somatostatin but not that induced by SMS 201-995. Finally, tolerance developed to the grooming-inducing effect of SMS 201-995 and somatostatin. In addition there was cross tolerance between somatostatin and SMS 201-995.

Microinjection of anti-vasopressin serum into limbic structures of the rat brain: effects on passive avoidance responding and on local catecholamine utilization

Rats which had received bilateral microinjections of 1:50 diluted anti-vasopressin serum into the dorsal or ventral hippocampus, immediately after the learning trial of a one-trial passive avoidance test, showed a reduction in avoidance latency scores during subsequent retention tests 24 and 48 h later. Postlearning microinjection of anti-vasopressin serum into either the dorsolateral septum or the caudate nucleus was without effect on the retention of passive avoidance behavior. Microinjection of anti-vasopressin serum 1 h before the 24-h retention session into either the dorsal hippocampus, the ventral hippocampus or the dorsolateral septum attenuated avoidance responding during both the 24-h and 48-h retention sessions, whereas preretention microinjection of the serum into the caudate nucleus was not effective. Intracerebroventricular administration of the anti-vasopressin serum in amounts similar to those used in the microinjection experiments did not affect retention scores when given either immediately after the learning trial or before the first retention session. One week after the behavioral experiments, a repeated microinjection of anti-vasopressin serum decreased the local alpha-methyl-p-tyrosine methylester (alpha-MPT)-induced disappearance of noradrenaline in the ventral hippocampus and the dorsal hippocampus respectively. Microinjection of the antiserum in the dorsolateral septum enhanced noradrenaline disappearance in this brain region. No effect was found on alpha-MPT-induced dopamine disappearance in the caudate nucleus following local microinjection of anti-vasopressin serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurotensin suppresses ACTH-induced grooming

Abstract Neurotensin, a neuropeptide which exerts various behavioural effects, suppresses ACTH-induced grooming. The time course of this effect of neurotensin reveals that the peptide acts on the early portion of ACTH-induced grooming. This finding suggests that the suppressive effect of neurotensin on ACTH-induced grooming is different from that of neuroleptics.