D. de Wied

Behavioral effects of intraventricularly administered vasopressin and vasopressin fragments

Abstract Vasopressin is involved in memory processes. A single subcutaneous injection of arginine-8-vasopressin (AVP) increases resistance to extinction of a pole jumping avoidance response. This effect can also be achieved after a single intraventricular administration of much lower amounts than after systemic injection. The covalent ring of AVP, pressinamide (PA), is also highly active following intraventricular administration while the C-terminal part prolyl-arginyl-glycinamide (PAG) is less active. These results indicate that the covalent ring of vasopressin contains the essential requirements for the behavioral effect of this neurohormone. A second activity site however may be present in the C-terminal portion of the molecule.

Inhibitory effect of ACTH and related peptides on extinction of conditioned avoidance behavior in rats.

SummaryACTH, administered during extinction, delays extinction of an avoidance response in rats. To study structure activity relationships, the rate of extinction of an avoidance response performed in a shuttle-box and a pole jumping situation, was investigated in rats treated during the extinction period with ACTH (A3 peptide), synthetic ACTH β 1-24, β-MSH, α-MSH, ACTH 1-10, ACTH 5-10, and ACTH 11-24, administered as long acting zinc phosphate preparations. Zinc phosphate complex and protamine zinc insulin (PZI) were used as placebo control substances. It appeared that ACTH and related peptides significantly delayed the rate of extinction of the avoidance response. Full activity was obtained with ACTH 1-10 peptide while ACTH 5-10 was less active. ACTH 11-24 and PZI were without effect. These results were interpreted to indicate that the active part of ACTH in this respect is located in the N-terminal part of the molecule, presumably in the first 10 amino acids.Summary ACTH, administered during extinction, delays extinction of an avoidance response in rats. To study structure activity relationships, the rate of extinction of an avoidance response performed in a shuttle-box and a pole jumping situation, was investigated in rats treated during the extinction period with ACTH (A3 peptide), synthetic ACTH β 1-24, β-MSH, α-MSH, ACTH 1-10, ACTH 5-10, and ACTH 11-24, administered as long acting zinc phosphate preparations. Zinc phosphate complex and protamine zinc insulin (PZI) were used as placebo control substances. It appeared that ACTH and related peptides significantly delayed the rate of extinction of the avoidance response. Full activity was obtained with ACTH 1-10 peptide while ACTH 5-10 was less active. ACTH 11-24 and PZI were without effect. These results were interpreted to indicate that the active part of ACTH in this respect is located in the N-terminal part of the molecule, presumably in the first 10 amino acids.

Neuropeptides, food intake and body weight regulation: a hypothalamic focus

Energy homeostasis is controlled by a complex neuroendocrine system consisting of peripheral signals like leptin and central signals, in particular, neuropeptides. Several neuropeptides with anorexigenic (POMC, CART, and CRH) as well as orexigenic (NPY, AgRP, and MCH) actions are involved in this complex (partly redundant) controlling system. Starvation as well as overfeeding lead to changes in expression levels of these neuropeptides, which act downstream of leptin, resulting in a physiological response. In this review the role of several anorexigenic and orexigenic (hypothalamic) neuropeptides on food intake and body weight regulation is summarized.

PITUITARY–ADRENAL SYSTEM HORMONES AND BEHAVIOR

Neuropeptides related to ACTH, MSH and LPH are involved in acquisition and maintenance of conditioned behaviour. These peptides affect the behaviour by a temporary selective increase in the state of arousal in limbic midbrain structures, thereby increasing the motivational influence of environmental stimuli. Steroids of adrenal origin affect conditioned behaviour in a way opposite to that of ACTH and related peptides. Such steroids alter the arousal level in limbic midbrain structures to enhance discrimination and consequently the elimination of non relevant behaviourla responses. Neuropeptides related to ACTH play a basic role in motivational, learning and memory processes, while the pituitary-adrenal system through the secretion of corticosteroids has a secondary modulationg function.

The effects of ACTH- and vasopressin-analogues on CO2-induced retrograde amnesia in rats

Amnesia for a one-trial step-through passive avoidance response was induced in rats by application of CO2 until respiratory arrest occurred. The ACTH-analogue ACTH4–10 alleviated the amnesia when administered 1 hr prior to the retrieval test but not when given 1 hr prior to the acquisition trial. The behaviourally inert ACTH-analogue ACTH11–24 appeared to have no effect on the amnesia. The vasopressin-analogue desglycinamide lysine vasopressin (DG-LVP) antagonized the amnesia when administered 1 hr prior to the acquisition trial or 1 hr prior to the test trial. The relevance of these date to present theories on amnesia is discussed.

Dissociation of the behavioural and endocrine effects of lysine vasopressin by tryptic digestion

1 . Lysine vasopressin induces resistance to extinction of active avoidance behaviour (De Wied, 1971). 2 . Digestion of lysine vasopressin with trypsin almost completely destroys the pressor‐, antidiuretic‐, oxytocic‐ and corticotrophin‐releasing factor activities of lysine vasopressin, but does not materially influence its effect on the maintenance of an avoidance response.

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.

Behavioral effects of peptides

The pituitary—adrenal system plays an essential role in homeostatic functions. Numerous aspects of stress-induced pituitary—adrenal activation in relation to peripheral mechanisms of adaptation have been studied since Selye’s first observations on the general adaptation syndrome some 40 years ago (Selye, 1950). Little attention, however, has been paid to the brain as a target for these hormones. Clinical observations frequently commented on psychological changes in addition to electrophysiological alterations in hyper- as well as hypocorticism (Cleghorn, 1957; Von Zerssen, 1976). Many a laboratory experiment during the last decade, however, disclosed the implication of a number of pituitary and hypothalamic hormonal peptides on various brain functions. The importance of these entities was revealed by observations on behavioral disturbances following extirpation of the pituitary gland in rats (de Wied, 1969); in animals with hereditary diabetes insipidus, which lack the ability to synthesize vasopressin (de Wied et al., 1975a); or in rats in which the action of vasopressin in the brain is neutralized by intraventricular administration of specific vasopressin antiserum (van Wimersma Greidanus et al., 1975a).

Behavioral and endocrine responses of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain)

Behavioral and endocrine profiles were established of homozygous (HO-DI) and heterozygous (HE-DI) rats with hereditary hypothalamic diabetes insipidus in comparison to Wistar strain rats. HO-DI rats were inferior in acquiring and maintaining active and passive avoidance behavior. Behavioral deficits were most obvious in a step-through one-trial learning passive avoidance test and least in multiple trial one way active avoidance test. Plasma corticosterone levels determined after the retention test appeared to be closely related to the passive avoidance behavior of the HO-DI rats. Passive avoidance immediately after the single learning trial was associated with elevated plasma corticosterone level; absence of avoidance and absence in plasma corticosterone elevation was observed 24 hr after learning. These observations are compatible with the hypothesis that vasopressin is involved in the consolidation and/or retrieval of learned responses. Differences between HO-DI and Wistar rats in open field behavior, in response threshold to electric footshock, and in a number of somatic endocrine parameters are reported and discussed.

The influence of peptides derived from corticotrophin (ACTH) on performance. Structure activity studies.

Publisher Summary This chapter describes the influence of peptides derived from corticotrophin (ACTH) on performance. In the study reported in the chapter, two approaches are followed. First, it sought the small peptide sequence of ACTH that possesses essentially the same behavioral effects as ACTH itself. Second, the chapter tries to increase the behavioral potency of the sequence ACTH 4-9 by introducing certain structural modifications. Attention is focused on the dissociation between behavioral activity and melanocyte stimulating hormone (MSH)-like potency. The influence of peptides derived from ACTH on acquisition and extinction of conditioned avoidance behavior in rats was studied. The tetrapeptide ACTH 4-7 is found to be the short peptide that still bears the essential elements required for the behavioral effects. The improved performance of hypophysectomized rats treated with ACTH or fragments of ACTH is neither due solely to improved motor and/or sensory capacities nor to an increase in the level of general activity.