Thirst and memory

Author: Matteo Parola
Date: 25/03/2012


“Is there a possible relationship between the sense of thirst and the memory consolidation?”

Thirst is an homeostatic function of the human body. Its main and most understood effects are addressed to increase the water intake and to reduce the water loss of the organism. (water metabolism)
The objective of this research is to find evidences of the involvement of thirst in the enhancement of mnemonic processes.

Two thirst-related situations can be taken in consideration as responsible of memory improvement:
a) Hyponatremia, that is one of the main causes of thirst.
b) Synthesis of thirst-related peptides, that represent the response of the body to thirst.

Talking about hyponatremia, the evidences show a negative role of this condition. Studies conducted on
rats with moderate and severe hyponatremia indicated that they had significantly reduced step-through latency, indicating impairment in memory. This reduced step-through latency was improved by the treatment of tolvaptan (0.25-8 mg/kg daily doses), a vasopressin V(2) receptor antagonist.
Chronic hyponatremia impairs memory in rats, PubMed

However there are no evidences that a moderate hyponatremia can damage memory, so hyponatremia can now be excluded from the possible causes of memory improvement and we must consider the effects of thirst-related peptides.

Regardless the typology of thirst, the most important final pathway lead to the liberation of vasopressin.
Vasopressin is a posterior pituitary hormone involved in the regulation of water loss and intake.

It seems also that ADH has many important effects on the central nervous system, indeed :

  1. It has been implicated in memory formation, including delayed reflexes, image, short- and long-term memory, though the mechanism remains unknown. However, the synthetic vasopressin analogue desmopressin has come to interest as a likely nootropic
  2. Vasopressin is released into the brain in a circadian rhythm by neurons of the supraoptic nucleus
  3. Vasopressin released from centrally projecting hypothalamic neurons is involved in aggression, blood pressure regulation and temperature regulation
  4. Selective AVPr1a blockade in the ventral pallidum has been shown to prevent partner preference, suggesting that these receptors in this ventral forebrain region are crucial for pair bonding
  5. Recent evidence suggests that vasopressin may have analgesic effects. The analgesia effects of vasopressin were found to be dependent on both stress and gender

Vasopressin, Wikipedia

*Nootropics are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration.

Once found an association between thirst, peptides and memory, it’s necessary demonstrate temporal association between the sense of thirst and vasopressin secretion and the details of the mechanism of ADH action on central nervous system.

  • First of all it is necessary to demonstrate a temporal association between the sense of thirst and the vasopressin secretion.

In the image below are compared the levels of thirst, water intake and vasopressin production during the time. We can see that vasopressin reach its secretion peak at the same time that thirst reach its own maximum. So thirst and ADH secretions are temporally bound.

* The next step consist in demonstrating more precisely the correlation between vasopressin and memory enhancing

It was observed that mice lacking a functional vasopressin 1b receptor (Avpr1b) display decreased levels of aggression and social memory. In the article, they used Avpr1b-knock-out (Avpr1b(-/-)) mice to examine whether an abnormality of this receptor results in specific cognitive deficits in the domain of hippocampal function. Avpr1b(-/-) mice were deficient in sociability and in detecting social novelty, extending previous findings of impairment in social recognition in these mutants. Avpr1b(-/-) mice could recognize previously explored objects and remember where they were experienced, but they were impaired in remembering the temporal order of presentation of those objects. Consistent with this finding, Avpr1b(-/-) mice were also impaired on an object-odor paired associate task that involved a temporal discontiguity between the associated elements. Finally, Avpr1b(-/-) mice performed normally in learning a set of overlapping odor discriminations and could infer relationships among odors that were only indirectly associated (i.e., transitive inference), indicating intact relational memory. The Avpr1b is expressed at much higher levels than any other part of the brain in the pyramidal cells of hippocampal CA2 area, a subfield of the hippocampus that has physiological and genetic properties that distinguish it from subfields CA1 and CA3. The combined results suggest that the Avpr1b, perhaps in CA2, may play a highly specific role in social behavior and episodic memory

  1. In the overlying figure are shown performance of the Avpr1b / and WT mice on object recognition. A “What-where-when” memory task. B A difference score was used to assess preference for the older versus recent objects (“what” memory). Avpr1b / mice display significant “what”memory, but WT mice display a greater preference than the Avpr1b / mice. A difference score was also used to assess preference for the displaced versus the stationary object (“where” memory). Avpr1b / mice display significant “where” memory. In addition, a difference score was used to assess preference for the older stationary object versus the more recent objects (“when” memory). Avpr1b / mice do not display significant “when” memory
    Vasopressin 1b receptor knock-out impairs memory for temporal order

Most of the reseaches on the hippocampus were conducted by De Wield and collegues.
They discovered that hippocampal theta activity during paradoxical sleep plays a crucial role in the long-term storage of information in the brain of those mammals in which this EEG pattern is present; and endogenous vasopressin contributes to this process by means of its influence on this neuronal activity. Two ADH actions were found:
The neurotransmitter action of VP was characterized by an excitatory response (depolarized membrane associated with action potentials, or an increase in spontaneous activity) of rapid onset and relatively short duration once the applied peptide had been withdrawn; in contrast, its neuromodulating action involved a relatively long-lasting potentiation (enhancement) of the responsivity of the target neuron to its synaptic. In the studies reviewed herein, neuromodulatory action was exhibited as a VP induced long-lasting facilitation of glutamate -mediated excitatory neurotransmission in the lateral septum, dorsal hippocampus, and ventral hippocampus.

De Wied and Colleagues I: Evidence for a VP and an OT Influence on MP: Launching the “VP-OT Central Memory Theory”
De Wied and Colleagues III: Brain Sites and Transmitter Systems Involved in the Vasopressin and Oxytocin Influence on Memory Processing

In the human species hippocampus is probably the most important structure involved in declarative memory processes and it is especially implicated in the consolidation phase of learning.
So if this kind of vasopressin action exist also in the human species, it should be a perfect candidate to explain a correlation between thirst and memory.

Other experiments were conducted on Java monkeys:
The roles of vasopressin (arginine-vasopressin) in controlling conditioned operant food-procuring reflexes and various types of memory were studied in monkeys. Types of memory were: conditioned reflex, image (Hunter-Kerr test), short-term, and long-term. The effects of vasopressin were assessed in terms of objective measures of higher nervous activity: movement and autonomous functions. These studies showed that administration of vasopressin to monkeys had different effects on simple operant food-procuring responses and memory processes. Vasopressin had greater effects on memory processes and the restoration of memory after functional derangements of higher nervous activity. The question of the formation of the two types of effect of vasopressin on higher nervous activity is discussed in relation to the evolution of mammals.
The effects of vasopressin on memory processes in Java monkeys

The effects of vasopressin in human species are controversial.
Some researchers showed positive role of vasopressin, while others cannot confirm those evidence.
For example the study of Guastella AJ and collegues demonstered that administration of AVP to male humans enhances the encoding of both happy and angry social information to make this more memorable (vasopressin enhances the encoding of happy and angry faces in humans, 2010, PubMed)
Gais S et al. couldn.t find a positive role in memory consolidation, but their study found an EEG activity that indicated a significant arousing influence of VP. Results suggested that if VP affects memory function it might do so primarily at the stage of encoding of the materials to be learned.
Post-trial administration of vasopressin in humans does not enhance memory formation, 2002, PubMed.

At last a study leaded by Scholey AB in 2009 assessed that glucose enhancement of memory may therefore critically depend on participants' initial thirst, as we can see in the image.
This double-blind, placebo-controlled study examined the influence of appetitive state on glucose enhancement of memory
Glucose enhancement of memory depends on initial thirst.

The relationship between thirst and memory remains extremely hard to demonstrate. Surely we can say that a severe state of dehydratation is dangerous and harmful for memory, since it damage neurons. However there is the possibility that a state of moderate thirst can improve memory functions. This possibility is represented mainly by the effects of ADH on central nervous system and expecially on the hippocampus. Those effects unfortunately have been precisely identified only in other species and not in humans.
In the other hand human brain is more complex and so ADH effects are surely less evident. So, since evidences of a vasopressin effect in memory enhancing was found in many other species, it is probable that it shoul act also on human memory.
Nowadays it seems that the research is more interested in investigate other actions of ADH, expecially his effects on social recognition.

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