Acute THPVP inactivation decreases the glucagon and sympathoadrenal responses to recurrent hypoglycemia

Abstract

The posterior paraventricular nucleus of the thalamus (THPVP) has been identified as a forebrain region that modulates the central nervous system (CNS) response to recurrent experiences of stressors. The THPVP is activated in response to a single (SH) or recurrent (RH) experience of the metabolic stress of hypoglycemia. In this study, we evaluated whether temporary experimental inactivation of the THPVP would modify the neuroendocrine response to SH or RH. Infusion of lidocaine (LIDO) or vehicle had no effect on the neuroendocrine response to SH, comparable to findings with other stressors. THPVP vehicle infusion concomitant with RH resulted in a prevention of the expected impairment of neuroendocrine responses, relative to SH. LIDO infusion with RH resulted in significantly decreased glucagon and sympathoadrenal responses, relative to SH. These results suggest that the THPVP may contribute to the sympathoadrenal stimulation induced by hypoglycemia; and emphasizes that the THPVP is a forebrain region that may contribute to the coordinated CNS response to metabolic stressors.

Fig. 1

Bilateral guide cannula placement. Left, figure from Paxinos and Watson, 1986; the circle indicates the target area of the THPVP. Right, actual bilateral guide cannula placement. Cresyl violet stained coronal section showing cannula track (black arrow) and cannula end (green dye) marking the target area of the THPVP. (The specific placement coordinates for this micrograph correspond to −3.3 mm AP from bregma; ±0.2 mm ML from midline; −5.4 mm DV from skull.)

Fig. 2

Comparison of Glucagon, EPI, and NEPI responses to single or recurrent hypoglycemia with PBS or LIDO infusion into the THPVP. Upper: Glucagon, EPI, and NEPI responses to recurrent hypoglycemia (RH) are comparable to those in rats experiencing a single (naive) bout of hypoglycemia (SH), when PBS is infused into the THPVP. Data for RH subjects are expressed as a % of the identical, time-matched responses for SH subjects (all mean SH responses being set to ‘100%’), and are shown as mean±standard error of the mean. See Table 1 and Results for group sizes. Lower: Glucagon, EPI, and NEPI responses to RH are decreased relative to those of rats experiencing a single (naive) bout of hypoglycemia (SH), when LIDO is infused into the THPVP. Data for RH subjects are expressed as a % of the identical, time-matched responses for SH subjects (all mean SH responses being set to ‘100%’), and are shown as mean±standard error of the mean. See Table 1 for group sizes. ‘*’ indicates p<0.05 vs. SH response, at the timepoint indicated.

Fig. 3

Glucagon, EPI, and NEPI responses to recurrent hypoglycemia with PBS or LIDO infusion into the THPVP. THPVP LIDO suppresses the NEPI response to a third bout of hypoglycemia (RH), relative to THPVP PBS-infused RH subjects. Data for LIDO-infused subjects are expressed as a % of the identical, time-matched responses for PBS-infused subjects (all mean PBS responses being set to ‘100%’), and are shown as mean±standard error of the mean. See Table 1 for group sizes. ‘*’ indicates p<0.05 vs. PBS response, at the timepoint indicated.