Tj.B. Van Wimersma Greidanus

Evidence for the release of vasopressin and oxytocin into cerebrospinal fluid: measurements in plasma and CSF of intact and hypophysectomized rats.

Arginine-8-vasopressin (AVP) and oxytocin (OXT) were measured by radio-immunoassay (RIA) in cerebrospinal fluid (CSF) and plasma of Wistar rats under various conditions. In addition, basal plasma leve

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.

Effects of Systemic and Intracerebral Administration of Two Opposite Acting ACTH-Related Peptides on Extinction of Conditioned Avoidance Behavior

The effects of the decapeptide ACTH-(1–10) and [D-phe7]-ACTH-(1–10) were tested on the rate of extinction of a pole-jumping avoidance response in rats. ACTH-(1–10) in doses of 20, 50, and 100 µg inhibited extinction of the avoidance response 4 h following subcutaneous administration. [D-phe7]-ACTH-(1–10) in doses of 20, 50, and 100 µg facilitated extinction 4 h after injection. Intracerebral implantation of approximately 10 µg of these ACTH-analogues in the freely moving rat had similar effects on extinction of avoidance response when implanted into the region of the rostral mesencephalon and the caudal diencephalon, at the posterior thalamic level, or in the cerebrospinal fluid. Ineffective sites were the nucleus ventralis thalami, the nucleus anterior medialis thalami, the nucleus reuniens, the globus pallidus, the nucleus accumbens, the fornix, and the hippocampus. The results support the hypothesis that the site of action of ACTH and of ACTH-analogues on extinction of an avoidance response is localized in the central nervous system.

The role of limbic vasopressin and oxytocin in social recognition

Young male rats were exposed two times for 5 min, to older male rats with an interval of 30 min in the anti-vasopressin serum experiments and with an interval of 120 min in the anti-oxytocin serum experiments. The time spent by the older rats with social investigation of the younger animal was scored during the two encounters. In placebo-treated animals the time spent on social investigation of the younger animal during the second encounter at 30 min is significantly shorter than during the first one (social recognition). However, intracerebroventricular or local application of anti-vasopressin serum in the dorsal or ventral hippocampus or in the dorsal septal area, but not in the n. olfactorius, results in similar periods of time spent for social investigation during the two encounters. Thus, endogenous vasopressin in the dorsal and ventral hippocampus and in the dorsal septal region plays a physiological role in social recognition/memory. In placebo-treated rats the time spent on social investigation of the younger animal during the second encounter at 120 min is similar to that during the first encounter. However, local administration of anti-oxytocin serum in the ventral hippocampus, but not in the dorsal hippocampus, nor in the n. olfactorius or the septal area, results in shorter investigation times during the second encounter. Thus, taken together the presence or local release of vasopressin and oxytocin in the ventral hippocampus and that of vasopressin (but not oxytocin) in the dorsal hippocampus and dorsal septal area are of physiological importance for social recognition.

Histamine as an extremely potent releaser of vasopressin in the rat

Intraperitoneal and intraventricular injection of histamine induces a very fast and high elevation of vasopressin in rat plasma as determined by radioimmunoassay. The effects are dose and time related. The intraventricular injection is more effective with regard to time and dose than the intraperitoneal injection.

The Role of Vasopressin in Memory Processes

Publisher Summary This chapter discusses the role of Vasopressin in memory processes. During the last 10 years, evidence has accumulated that peptides from pituitary origin play an important role in acquisition and/or extinction of conditioned avoidance behavior. Administration of pitressin, a crude vasopressin preparation extracted from posterior pituitary tissue, induces resistance to extinction of a shuttlebox avoidance response. The principle present in pitressin responsible for this “long-term” effect seemed to be vasopressin and proof of this assumption was obtained in experiments in which a pole jump avoidance response was studied. The significance of vasopressin for the consolidation of learned behavior is also demonstrated by experiments in rats with hereditary hypothalamic diabetes insipidus (DI) that lack the ability to synthesize vasopressin. It appeared that homozygous DI rats in contrast to heterozygous littermates were unable to retain the passive avoidance response. Administration of vasopressin and vasopressin analogues induces resistance to the extinction of active and passive avoidance behavior.

Differential localization of the influence of lysine vasopressin and of ACTH 4-10 on avoidance behavior: a study in rats bearing lesions in the parafascicular nuclei.

A single subcutaneous injection of either 1.8 or5.4 µg lysine vasopressin (LVP) into parafascicular (pf) lesioned rats induced a dose-dependent preservation of a pole-jump shock avoidance response. The effect of the higher dose of LVP lasted for a minimum of 5 days whereas the effect of the lower dose was present for only 2 days. These results can be contrasted with the effect of 1.8 µg LVP in sham-operated rats in which the avoidance response is maintained for many days after injection. Daily subcutaneous administration of either 1 or 9 µg of the ACTH analogue (ACTH 4–10) to pf rats did not preserve the pole-jump response. However, in sham-operated animals, 1 or 3 µg ACTH 4–10 was effective in preserving the avoidance response in a dose-dependent way. Because ACTH 4–10 does not preserve avoidance behavior in pf-lesioned animals, the results of these experiments support the conclusion that the parafascicular area is essential for the behavioral effects of this peptide. In contrast, the fact that LVP is effective in lesioned animals (even though higher doses are required than are normally used), together with the earlier finding that local application of LVP in the posterior thalamic region results in a preservation of the avoidance response, indicates that LVP may have its site of action in the parafascicular area as well as in other brain structures.

Neurohypophyseal hormones and excessive grooming behaviour

The pattern of excessive grooming displayed by rats treated with vasopressin and oxytocin was investigated by calculating the frequencies and contribution of the behavioural elements head washing, body grooming, anogenital grooming, paw licking and scratching. In addition, the suppressive effect on peptide-induced grooming of the dopamine D1 receptor antagonist SCH 23390, of neurotensin and of the opiate receptor antagonists naloxone and naloxone-methobromide was studied. The pattern of excessive grooming induced by vasopressin and by oxytocin was characterized by the contribution of most behavioural elements to the total grooming scores. Oxytocin-induced excessive grooming was characterized by a marked increase in the frequency of anogenital grooming. SCH 23390, neurotensin and naloxone, but not naloxone-methobromide, suppressed excessive grooming induced by vasopressin and oxytocin. It is suggested that dopamine D1 receptors as well as opiate receptors located within the blood-brain barrier are involved in the excessive grooming induced by neurhypophyseal hormones.

Relationships between α-MSH levels in blood and in cerebrospinal fluid

Using a new cannulation technique of the cisterna magna of the rat, CSF was obtained in which α-MSH levels were determined under various conditions and were compared with a-MSH levels in plasma. Basal levels of 66 ± 9 pg α-MSH/ml were found in the CSF and of 179 ± 13 pg α-MSH/ml in the plasma. A rapid flow of CSF from the lateral ventricles to the cisterna magna could be established as detected by elevated α-MSH levels in cisternal CSF 2 min after injection of a large quantity of α-MSH into the ventricular system. A half-time disappearance of α-MSH from the CSF of 33 min was calculated. The possibility of a contribution of peripheral α-MSH to central melanotropic activity was suggested by the finding of elevated levels of α-MSH in the CSF, following artificially induced high α-MSH concentrations in the blood. Additionally, the movement of α-MSH from the CSF to the blood was demonstrated. Both these movements were shown to be independent of the pituitary gland, since hypophysectomized animals exhibited the same rate of α-MSH transport as intact animals.

Effects of Steroids on Extinction of an Avoidance Response in Rats.: A Structure–Activity Relationship Study

Publisher Summary This chapter discusses the effects of steroids on the extinction of an avoidance response in rats. The effect of adrenocortical steroids on the extinction of the conditioned avoidance response (CAR) might be the result of glucocorticoid activity rather than of mineralocorticoid activity, because the effect of aldosterone on extinction is small. ACTH exhibits an opposite effect—that is, it delays extinction of the CAR. The facilitating effect of dexamethasone and corticosterone on extinction of the CAR, however, is not caused by inhibition of pituitary ACTH release because the steroids also facilitate extinction of the CAR in hypophysectomized animals. This shows that metabolites of progesterone are also effective in suppressing a conditioned avoidance performance of rats. This suggests that the effect of steroids on extinction of the CAR is not specific for adrenocortical hormones. The purpose of the experiments described in the chapter was to determine the relationship between structure and behavioral activity by using various chemically related steroids.