The mechanism by which (1S,3R)-ACPD, a metabotropic glutamate receptor agonist, induces burst firing in lateral septal neurons of the rat was investigated in coronal brainstem slices. Membrane currents were characterized in voltage clamp using whole-cell recordings. In the presence of (1S,3R)-ACPD, following depolarizing voltage jumps, repolarization towards the holding potential generated an inward aftercurrent. It could have a plateau-like phase and decayed exponentially. This (1S,3R)-ACPD-dependent inward aftercurrent was accompanied by an increase in cell conductance and was reduced following partial replacement of extracellular sodium by N-methyl-d-glucamine. It was unaffected by TEA or barium, and persisted in Cs-loaded neurons or following partial replacement of extracellular chloride by isethionate. This suggests that it was mainly carried by sodium. Loading neurons with the calcium chelator, BAPTA, or blocking transmembrane calcium currents, suppressed the (1S,3R)-ACPD-dependent aftercurrent. By contrast, partial replacement of extracellular sodium by lithium did not affect it. Thus, this current was dependent upon calcium influx but was not due to a sodium/calcium exchanger. It was probably mediated by G protein activation. Indeed, in neurons loaded with GTP-γ-S, following depolarizing voltage jumps, repolarization towards the holding potential revealed an inward aftercurrent having properties similar to those of the (1S,3R)-ACPD-dependent current. We suggest that (1S,3R)-ACPD induced calcium-activated non-selective channels. In the presence of this agonist, a depolarization-evoked calcium influx could thus evoke a cationic inward current. This current probably promotes the burst firing observed in lateral septal neurons in current clamp.

Biochemical investigations show that vasopressin interacts with noradrenalin to potentiate noradrenalin-induced accumulation of cyclic-AMP in the hippocampus, via the beta-adrenergic receptors. We previously showed in BALB/c mice that the effects of vasopressin (bilaterally injected at a 25-pg dose) in the ventral hippocampus were more effective than in the dorsal hippocampus on the retrieval and relearning of a Go-No Go visual discrimination task. Considering our results and those reported by biochemical investigations, we evaluated possible noradrenergic-vasopressinergic interaction in the ventral hippocampus under our behavioral conditions. To do so, we first explored the effects of propranolol and phentolamine, antagonists of beta- and alpha-adrenergic receptors, respectively. Second, we assessed the modifications in the vasopressin-induced improvement of retrieval and relearning by pretreating the subjects with either propranolol or phentolamine. Third, we tested the treatments in a locomotor activity task to determine whether the effects demonstrated in the two preceding experiments could be partially due to locomotor alterations by the drug. The results indicated that bilateral injection of propranolol (1 microgram on each side), which did not appear to affect the retention performance itself, completely blocked the enhancement of retrieval and relearning resulting from the vasopressin treatment. In contrast, bilateral injection of phentolamine (1 microgram on each side), which moderately improved retrieval, enhanced the vasopressin effect. The present results lend further support to the view that both noradrenalin and vasopressin play important roles in retrieval and relearning processes. More importantly, they provide additional support for the functional interaction of the noradrenergic and vasopressinergic hippocampal systems.

The HIV and visna lentiviruses induce an inflammatory reaction in the central nervous system (CNS) of the infected hosts leading to dysmyelination, demyelination, and neuronal loss. The basic domain of the transactivating Tat protein has been involved in CNS damage. Infusion of basic containing domain Tat peptides in the lateral ventricle (systemic injection) or in the grey matter, i.e., hippocampus and thalamus (local injection), induced an inflammatory process characterized by the formation of an edema and invasion of macrophage accompanied by reactive astrogliosis. Control peptides originating from either lentiviral proteins or irrelevant protein as ovalbumin did not lead to any inflammatory reaction or cell death. The inflammation led to the loss of ependymal cells in the lateral ventricles and neurons in the grey matter. RNA extracted from the Tat-injected hemisphere reacted with TNF-α, IL-1α and β, and IL-6 probes. The macrophage/microglia inducible nitric oxyde synthase was also expressed. Blockade of TNF-α by a pentoxifylline treatment led to the decrease of IL-1 and iNOS expression accompanied by a reduction of the volume of the lesions indicating that the Tat-induced lesions might be mediated by TNF production.

Previous results have indicated the involvement of the hippocampus in the behavioral effect of vasopressin, with a better effect when the peptide was injected in the ventral part rather than in the dorsal part of this structure. The purpose of the present study was to determine, in mice, whether the injection of vasopressin or vasopressin antisera into the ventral hippocampus has an effect on retrieval and relearning of a Go-No Go visual discrimination task and, if so, to what extent this involvement of the vasopressin system depends on the integrity of the medial amygdaloid nucleus, the main source of vasopressin innervation in the ventral hippocampus in rats. In the first experiment, we showed that pretest microinjection of Arg8-vasopressin (25 pg per animal) in the ventral hippocampus alleviated forgetting observed after a prolonged interval of 24 days between the acquisition of information and its retrieval. This enhancing effect was characterized by better retrieval and relearning in vasopressin-treated mice than those in control mice. Conversely, an immunoneutralization of endogenous vasopressin in the ventral hippocampus by the microinjection of vasopressin antisera (1/10 dilution) resulted in the drastic impairment of retrieval and relearning. Since the lack of an observable change in a locomotor activity test might explain these results, we postulated that the vasopressin system in the ventral hippocampus is involved in retrieval processes. Moreover, the effects of these treatments in a nonassociative context suggest that the effect of vasopressin could be dependent on the contextual paradigm used. In the second experiment, we localized vasopressin immunoreactive fibers in the CA1-CA2 ventral hippocampal fields and CA4-gyrus dentatus region, and vasopressin perikarya in the medial amygdaloid nucleus. Then, the projection of vasopressin cells from the medial amygdaloid nucleus to the ventral hippocampus was evaluated by studying changes in vasopressin immunoreactive fiber density in the ventral hippocampus after a lesion of the medial amygdaloid nucleus. The results showed the almost complete disappearance of vasopressin fibers in the CA1-CA2 hippocampal fields after the medial amygdaloid lesion. In contrast, vasopressin fibers in the CA4 and gyrus dentatus region remain unchanged. On the basis of our immunohistochemical results, our third experiment tested the repercussions of the change in vasopressin innervation in the ventral hippocampus, due to the medial amygdaloid lesion, on the effects of exogenously administered vasopressin on both retrieval and relearning processes. The medial amygdaloid lesion induced a deleterious effect on retrieval without really affecting the ability to relearn. No observable change in locomotor activity could explain this impairment.(ABSTRACT TRUNCATED AT 400 WORDS)

It is now an established fact that for a variety of species, neuropeptides play an important role in the control and expression of certain behavior. Examples are found in rodents, in which drinking is activated by angiotensin II, maternal behavior is accelerated by oxytocin, feeding is inhibited by bombesin and cholecystokinin, stereotyped grooming is induced by ACTH, and lordotic behavior is inhibited by vasopressin. Some of these neuropeptides, such as ACTH and vasopressin, can induce behavioral changes which result from the action of more complex processes than those at play in the behaviors mentioned above. These processes are the ones involved in learned behaviors. In this case, these neuropeptides not only contribute to the control and expression of pre-programmed physiological behaviors, but are also involved in the acquisition and retention of new behaviors. In other words, certain neuropeptides are assumed to act in learning and retention processes, although the nature of their action is not yet known. Indeed, a process as complex as memory results from the interaction of numerous factors including the subject's motivational, emotional, and arousal states, which can directly or indirectly act upon the neural support of memory processes. Moreover, the nature of the information conveyed in these neural circuits depends on the interaction of certain molecules and/or on their neuromodulation. This makes it difficult to determine whether neuropeptides affect learning, memory consolidation and retention: (i) by activating the emotional and arousal states which produced the optimal conditions for learning, memory storage and retrieval; (ii) by acting directly upon the neural circuit involved in these memory processes, or (iii) by a combination of the two. Following the pioneering work by De Wied nearly twenty years ago, many studies have shown that arginine-vasopressin (AVP) affects many behaviors, especially learned ones. AVP is a posthypophysial nonapeptide known to be an antidiuretic and pressor hormone. Its biosynthesis /121,130,135,136/ takes place mainly in the supraoptic and paraventricular nuclei of the hypothalamus /139/. It is secreted and stored in the posterior hypophysis. From there, it is released into the systemic circulation in response to Cadependent action potentials /147/. The magnocellular vasopressinergic neurons of the hypothalamic nuclei and their projections to the neurohypophysis constitute the main component of the classic endocrine hypothalamusneurohypophysial pathway /119/. The pressor and antidiuretic activities of AVP are currently well known /43,151/ and its endocrine effects are mediated through receptors on target organs, including VI receptors on smooth muscle cells lining blood vessels associated with the pressor response /125/, and V2 receptors in the kidney which are essential for the renal antidiuretic actions of AVP /39/. It gradually became known that in addition to the fibers originating in the hypothalamic nuclei which make up the hypothalamus-neurohypophysial pathway, there are also vasopressinergic fibers in numerous cerebral regions in the guinea-pig 1621, rat /30,141/, and mouse /42/, ranging from the olfactory bulb to the spinal cord, in addition to vasopressinergic neuron groups in the septal region /140/, the bed nucleus of the stria terminalis, the medial amygdaloid nucleus, and the locus coeruleus /51,140/. These vasopressinergic pathways, called extrahypothalamic pathways, are shown in Figure 1, in which we can see that the projections of certain vasopressinergic neuron groups and the origins of certain vasopressinergic fibers are unknown. The vasopressinergic receptors detected in the brain are

Antiserum to [Arg8]vasopressin (anti-AVP) was bilaterally administered into dorsal hippocampus at 1:50 or 1:10 dilution 20 min before the 24-day retention session of a visual discrimination task. This treatment by itself did not affect the retention performance by comparison with the respective control group, whatever the dilution of anti-AVP, suggesting that hippocampal endogenous AVP is not involved in our behavioral paradigm. On the other hand, intracerebroventricular (i.c.v.) administration of AVP 10 min before the retention session improved retention performance of the visual discrimination task. When anti-AVP was injected at the 1:10 dilution into the dorsal hippocampus 10 min before the i.c.v. administration of AVP, the retention performance was not improved. These data suggest the involvement of the hippocampus in the behavioral expression of AVP following an i.c.v. treatment.

Pre-test local microinjection of arginine-vasopressin (AVP) into dorsal or ventral hippocampus resulted in an improvement of retention performance in an appetitively motivated task. Nevertheless, a better improvement appeared when AVP treatment was performed into ventral hippocampus suggesting a higher sensitivity of this part of hippocampus to the action of AVP. To examine a non-specific behavioral action of the peptide, the effect of AVP treatment on locomotor activity was assessed. When the treatment was given into ventral hippocampus, a reduction of locomotor activity was recorded, whereas after AVP injection into dorsal hippocampus, the peptide failed to alter locomotor activity.