Sodium intake by hyperosmotic rats treated with a GABAA receptor agonist into the lateral parabrachial nucleus

Abstract

Inhibitory mechanisms in the lateral parabrachial nucleus (LPBN) and central GABAergic mechanisms are involved in the regulation of water and NaCl intake. Besides increasing fluid depletion-induced sodium intake, the activation of GABA(A) receptors with muscimol into the LPBN also induces ingestion of 0.3 M NaCl in normonatremic, euhydrated rats. It has been suggested that inhibitory mechanisms activated by osmotic signals are blocked by GABA(A) receptor activation in the LPBN, thereby increasing hypertonic NaCl intake. Therefore, in the present study we investigated the effects of muscimol injected into the LPBN on water and 0.3 M NaCl intake in hyperosmotic cell-dehydrated rats (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. In euhydrated rats, muscimol (0.5 nmol/0.2 microl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (24.6+/-7.9 vs. vehicle: 0.5+/-0.3 ml/180 min) and water (6.3+/-2.1 vs. vehicle: 0.5+/-0.3 ml/180 min). One hour after intragastric 2 M NaCl load (2 ml), bilateral injections of muscimol into the LPBN also induced 0.3 M NaCl intake (22.1+/-5.2 vs. vehicle: 0.9+/-0.8 ml/210 min) and water intake (16.5+/-3.6 vs. vehicle: 7.8+/-1.8 ml/210 min). The GABA(A) antagonist bicuculline (0.4 nmol/0.2 microl) into the LPBN reduced the effect of muscimol on 0.3 M NaCl intake (7.1+/-2.1 ml/210 min). Therefore, the activation of GABA(A) receptors in the LPBN induces ingestion of 0.3 M NaCl by hyperosmotic cell-dehydrated rats, suggesting that plasma levels of renin or osmolarity do not affect sodium intake after the blockade of LPBN inhibitory mechanisms with muscimol.

Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride intake during cell dehydration

“…Similar to previous reports [16,20,31], the LPBN injection sites were centered in the central lateral and dorsolateral portions of the LPBN. Figure 1 shows the typical LPBN injection sites.…”

“…In a recent study [20], the authors also showed that the blockade of LPBN inhibitory mechanisms by injections of muscimol in this area also induced 0.3 M NaCl intake in fluid replete rats and in rats treated with intragastric 2 M NaCl load, suggesting that the increase in plasma osmolarity subsequent to NaCl ingestion does not appear to prevent further salt intake when GABA A receptors in the LPBN are activated.…”

“…Previous studies have shown that the blockade of LPBN inhibitory mechanisms by injections of methysergide or moxonidine combined with an increase in plasma osmolarity (intragastric load of 2 M NaCl) induced an unexpected ingestion of hypertonic NaCl [17,18], a clear paradox considering that 2 M NaCl load usually suppresses sodium appetite [19]. In addition, a previous study showed that activation of GABA A receptors into the LPBN induced 0.3 M NaCl intake in cell-dehydrated rats, suggesting that the increase in plasma osmolarity subsequent to NaCl ingestion does not appear to prevent further salt intake when GABA A receptors in the LPBN are activated [20]. …”

Variable effects of parabrachial nucleus lesions on salt appetite in rats depending upon experimental paradigm and saline concentration.

“…Comparably large water intakes after sc PEG, and enhanced intakes of 0.4 M NaCl after DOCA treatment, also have been observed in rats with capsaicin-induced destruction of peripheral sensory nerves (Curtis & Stricker, 1977). Furthermore, very large intakes of 0.3 M NaCl by rats have been observed after bilateral injection of various drugs into the lateral PBN in combination with systemic injection of hypertonic saline and other dipsogens (Kimura et al, 2008; Menani, De Luca, Thunhorst, & Johnson, 2000), as if the normal inhibition of salt appetite had been removed (see review by Stricker, 2004). Similarly, rats with ibotenic acid-induced lesions of the LPBN consumed relatively large amounts of water in one-bottle tests when they were injected with AngII but not with hypertonic saline (Edwards & Johnson, 1991; see also Ohman & Johnson, 1986).…”

Mapping and signaling of neural pathways involved in the regulation of hydromineral homeostasis

“…The activation of GABA A receptors by muscimol (a GABA A agonist) injected into the LPBN induces the ingestion of water and 0.3 M NaCl solution in both euhydrated and hyperosmotic cell-dehydrated rats, with the effect on sodium intake being reversed by the administration of bicuculline, a GABA A antagonist 34.…”