B. Bohus

Oxytocin, vasopressin and memory: opposite effects on consolidation and retrieval processes

The observation that administration of pitressin, a relatively crude extract of the neurohypophysis, during acquisition resulted in a long lasting resistance to extinction of a shuttle-box avoidance response led us to suggest that hypothalamo-neurohypophyseal principles affect memory processes 11. Subsequent studies showed that vasopressin was responsible for the long-term effect on avoidance behavior3, s. Timegradient studies with vasopressin favoured the hypothesis that consolidation processes are facilitated by the peptide s. The consolidation hypothesis has been corroborated by studies on passive avoidance 1 and approach behavior a and by the anti-amnesic effect of vasopressin, analogs and fragmentsla,~4,19,2L Since preretention administration of the peptide also facilitates passive avoidance behaviod, 5, increases resistance to extinction of active avoidance 5,s and approach responses 15 and vasopressin alleviates amnesia, when given prior to the retention test 7,19, the peptide may also enhance retrieval processes. Oxytocin, the other neurosecretory product of the hypothalamo-neurohypophy seal system also affects the maintenance of avoidance responses but it has an effect opposite to that of vasopressin 6,2°. Observations in particular with intracerebroventricular administration of oxytocin suggested that this peptide may be a naturally occurring amnesic neuropeptide 6. This hypothesis is obviously untenable unless timegradient effects which are typical for amnesic treatments are demonstrated. Accordingly, the present experiments were aimed to investigate the effects of oxytocin administered intracerebroventricularly at various intervals after the learning trial on the retention of a passive avoidance response. For comparison, the effects of similarly administered arginine-vasopressin (AVP) were also studied. Male SPF Wistar rats (Cpb, TNO, Zeist, The Netherlands), weighing 160-180 g, were used. The rats had free access to food and water and were kept under controlled light-dark conditions (light on between 5.00 and 19.00 h). For intracerebroventricular treatment a polyethylene cannula was implanted in a lateral ventricle under anesthesia

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.

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 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.

Effect of lysine, vasopressin and ACTH4-10 on conditioned avoidance behavior and hypophysectomized rats

The influence of lysine vasopressin (LVP) andACTH4–10 treatment on avoidance acquisition in a shuttle-box was studied in hypophysectomized rats. Both peptides restored the impaired avoidanc

Decreased serotonin turnover in the dorsal hippocampus of rat brain shortly after adrenalectomy : Selective normalization after corticosterone substitution

Pargyline-induced accumulation of serotonin (5-HT) was used as an index of 5-HT turnover rate in the dorsal hippocampus. One hour after bilateral removal of the adrenals, 5-HT turnover was significantly reduced when compared to that of the sham-operated controls. A low dose of corticosterone given immediately after adrenalectomy restored the 5-HT response, while the same dose of dexamethasone was ineffective. Pretreatment with dexamethasone blocked the 5-HT response to corticosterone in the acutely adrenalectomized rat. The specificity of the 5-HT response in the hippocampus corresponds to the properties of the glucocorticoid receptor system in rat hippocampal neurons.

Inhibitory and Facilitatory Effect of Two Related Peptides on Extinction of Avoidance Behavior

The polypeptide chain which constitutes the first ten amino acids of the ACTH molecule inhibits extinction of a shuttle-box avoidance response. If the phenylalanine molecule in the 7th position of this peptide is replaced by its dextrorotatory form, extinction is facilitated.

Adrenal steroids and extinction behavior: Antagonism by progesterone, deoxycorticosterone and dexamethasone of a specific effect of corticosterone☆

Abstract Extinction behavior was nearly absent in rats adrenalectomized one hour prior to forced extinction of a passive avoidance response. A low dose of corticosterone administered immediately after adrenalectomy normalized extinction behavior. Progesterone, 11-deoxycorticosterone and the synthetic glucocorticoid dexamethasone were not effective at the same or ten times higher doses. Instead, pre-treatment with these steroids prevented the normalizing effect of corticosterone on extinction behavior. These characteristics of steroid effects on behavior correspond to the strict specificity of the corticosterone receptor system in hippocampal neurons. The agonist or antagonist interaction of naturally occurring adrenal steroids with brain cells may serve behavioral adaptation.

Effects of vasopressin on active and passive avoidance behavior.

Male rats were trained in an active avoidance and/or a “step-through” type of passive avoidance situation. Lysine vasopressin administration resulted in resistance to extinction of active avoidance behavior if it was injected 1 hr prior to the third and final acquisition session; peptide treatment 6 hr prior to this session did not affect extinction. Resistance to extinction of passive avoidance behavior was also obtained when lysine vasopressin was injected 1 hr prior to the first retention trial on Day 3 of training. Peptide administration 6 hr prior to this trial appeared to be ineffective. If rats were trained in both the active and passive avoidance situation spaced 6 hr apart, lysine vasopressin only affected extinction of the particular behavior tested 1 hr after the single administration of peptide. The behavioral effects of lysine vasopressin evidently depend upon the time of treatment. No evidence of generalization was observed even though both behavioral responses were aversively motivated.

Effect of desglycinamide-lysine vasopressin (DG-LVP) on sexually motivated T-maze behavior of the male rat

Abstract Desglycinamide lysine vasopressin (DG-LVP), a vasopressin analog which has been found to facilitate the maintenance of active and passive avoidance behavior, influences the retention of a sexually motivated choice behavior of male rats in a T maze. A higher percentage of rats receiving DG-LVP after each acquisition session shows a correct choice during free-choice retention trials. The total number of correct choices is also higher than in the controls. Copulation reward after a correct choice is an essential requisite for acquiring the choice response and retention effect of DG-LVP. Male rats which were prevented from copulating with the receptive female goal rat or which were presented with another male in the goal box did not acquire the response, and their behavior was not influenced by DG-LVP. Response latencies were never affected by the peptide. It is concluded that the long-term effect of vasopressin on learned behavior is of a rather general nature and is most probably due to facilitated memory consolidation processes.