Elsevier

Neuroscience

Volume 158, Issue 2, 23 January 2009, Pages 833-844
Neuroscience

Neuropharmacology
Presence of α-1 norepinephrinergic and GABA-A receptors on medial preoptic hypothalamus thermosensitive neurons and their role in integrating brainstem ascending reticular activating system inputs in thermoregulation in rats

https://doi.org/10.1016/j.neuroscience.2008.10.038Get rights and content

Abstract

Thermal messages are relayed to the medial preoptic O-anterior hypothalamus (mPOAH) via the ascending reticular activating system (ARAS). According to previous findings that norepinephrine (NE)-ergic and GABA (gamma-amino butyric acid)-ergic inputs convey thermal information to the CNS, those neurotransmitters may be responsible for reciprocal correlation between body temperature and mPOAH warm-(WSNs) and cold-(CSNs) sensitive neuronal firing rates for thermoregulation. In this study on Wistar rats, we have characterized in vivo the role of α-1 NE-ergic and GABA-A receptors in the possible modulation of ARAS inputs to the thermosensitive neurons in the mPOAH. Nine WSNs, 7 CSNs and 19 thermo-insensitive neurons were recorded from mPOAH and effects of ARAS stimulation and iontophoretic application of prazosin as well as picrotoxin on those neurons were evaluated. The WSNs were excited by ARAS stimulation but inhibited by both prazosin and picrotoxin; whereas the CSNs were inhibited by ARAS stimulation and prazosin, but excited by picrotoxin. The NE excited the WSNs as well as the CSNs, while GABA had opposite effects on them, suggesting that NE and GABA interact in the mPOAH for thermoregulation. The findings unravel an intriguing possibility that in the mPOAH, GABA simultaneously acts on hetero-receptors located at pre-and post-synaptic sites, modulating the release of NE on the WSNs and CSNs for thermoregulation. Further, ARAS stimulation-induced similar excitatory and inhibitory responses of the WSNs and the CSNs support such converging inputs on these neurons for thermoregulation.

Section snippets

Experimental procedures

Male Wistar rats (n=33) weighing 250–300 g, housed individually under controlled 12-h light/dark conditions (lights on 7:00 AM to 7:00 PM) were used in this study. Experiments were approved by the University's Institutional Animal Ethics Committee and conformed to the NIH guidelines on the ethical use of animals. In this study, minimal number of animals has been used and best efforts were made to minimize their sufferings.

Urethane (1 g/kg) anesthetized rats were placed on a stainless steel

Results

We studied the effects of prazosin (an α-1 NE-ergic receptor antagonist), picrotoxin (a GABA-A receptor antagonist) and brainstem ARAS stimulation on temperature-sensitive neurons (WSNs and CSNs) and ISNs located in the mPOAH. A total of 35 neurons were recorded; 9 WSNs (25.72%), 7 CSNs (20%) and 19 ISNs (54.28%). The mean firing rate of the thermosensitive neurons correlated significantly with the rectal temperature while that of ISNs did not (Fig. 2A). In two separate studies we have already

Discussion

In this study, we registered 25.72% WSNs, 20% CSNs and 54.28% ISNs, which is generally in agreement with previous reports in rats (Jha et al 2001a, Mallick et al 2002, Mallick et al 2004), rabbits (Boulant and Demieville, 1977) and cats (Parmeggiani et al., 1987). NE and GABA both have been reported to modulate the spontaneous firing rate of thermosensitive neurons in the hypothalamic nuclei (Jha et al 2001a, Mallick et al 2002). In this study also, we observed that prazosin, an α-1 NE-ergic

Conclusions

NE excites both WSNs and CSNs, while GABA inhibits CSNs. The action of NE on WSNs and of GABA on CSNs might involve direct modulation of thermosensitive neurons by these neurotransmitters acting on α-1 NE-ergic receptors and GABA-A receptors, respectively, located post-synaptically on the thermosensitive neurons. On the other hand, the excitation of WSNs by GABA is possibly a result of its depolarizing effect by acting on GABA-A hetero-receptors located on NE-ergic pre-synaptic terminals at the

Acknowledgments

Funding to B.N.M. from Council of Scientific and Industrial Research and Department of Biotechnology, India is duly acknowledged.

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