Research report Evidence for a A-opioid–opioid connection between the paraventricular nucleus and ventral tegmental area in the rat Joseph G. Quinn a , Eugene O’Hare a , Allen S. Levine b , Eun-Mee Kim a, * a School of Psychology, University of Ulster at Jordanstown, Shore Road, Newtownabbey, Co. Antrim BT37 0QB, Northern Ireland, UK b Minnesota Obesity Center, V.A. Medical Center, Research Service (151), One Veterans Drive, Minneapolis, MN 55417, USA Accepted 18 August 2003 Abstract The paraventricular nucleus (PVN) and the ventral tegmental area (VTA) have been shown to be involved in opioid mediated feeding behavior. The present study examined whether A-opioid signalling between the PVN and VTA affected feeding behavior. Male Sprague– Dawley rats were cannulated with one cannula placed in the PVN and two cannulae placed in the VTA, which allowed for co-administration of the A-opioid receptor agonist [D-Ala 2 , NMe-Phe 4 , Gly-ol 5 ]-enkephalin (DAMGO) in one site and the opioid antagonist naltrexone (NTX) in the other site. Bilateral administration of DAMGO (1.2, 2.4 and 4.9 nmol) into the VTA stimulated feeding dose dependently at 2.4 and 4.9 nmol ( P < 0.05). The DAMGO (2.4 nmol)-induced increase of food intake following injection into the PVN was blocked by bilateral injection of NTX (6.6, 13.2 and 26.5 nmol) into the VTA at 2 and 4 h ( P < 0.05). In the reverse situation, the DAMGO (2.4 nmol)-induced increase of food intake following injection into the VTA was blocked by injection of NTX (13.2 and 26.5 nmol) into the PVN at 2 and 4 h ( P < 0.05). The present study suggests that a bidirectional A-opioid– opioid signalling pathway exists between the PVN and the VTA which influences feeding. D 2003 Elsevier B.V. All rights reserved. Keywords: Opioid; DAMGO; Paraventricular nucleus 1. Introduction Several studies have shown that the paraventricular nucleus (PVN) [6,12,15,22,25] and the ventral tegmental area (VTA) [1 – 3,9,18,19] are involved in opioid mediated feeding behavior. Administrations of opioid receptor ago- nists into the PVN [6,12,13,15,22] or VTA [1,7,17 – 19] have resulted in increased food intake; conversely admin- istrations of opioid antagonists into the same brain regions have resulted in decreased feeding responses [10,11,20,23, 25]. Previous studies have suggested that A-opioid receptor ligands such as the A agonist [D-Ala 2 , NMe-Phe 4 , Gly-ol 5 ]- enkephalin (DAMGO) and non-selective antagonists, such as naltrexone (NTX) or naloxone (NX) are potent regulators of feeding behavior in rats when injected into the PVN [10,25] or VTA [1,11]. DAMGO injection into the PVN significantly increases feeding in satiated rats, and admin- istration of NTX or NX into the PVN significantly decreases food intake in food-deprived rats [10,25] and in 2-deoxy-D- glucose (2-DG)-induced hyperphagic rats [10]. Injection of DAMGO into the VTA has been shown to increase the amount of time spent eating, increase the number of feeding bouts, and decrease the latency to begin feeding in satiated rats [1] and in food deprived rats [19]. In addition, bilateral injections of DAMGO into the VTA have been shown to significantly increase food intake [11,14]. Injection of NX into the VTA decreases consumption of sweet solutions in normally fed rats and food-restricted rats [21]. DAMGO induced-feeding in the VTA is reduced by co-administration of NTX into the VTA, or by subcutaneous injection [20]. The PVN plays a key role in food intake and energy homeostasis, while the VTA has long been associated with reward-related processing [24]. There is evidence to suggest that there is a direct or indirect neuroanatomical connection between the PVN and the VTA [8,16], and the PVN sends fibres through forebrain bundles that terminate in the VTA [8]. The present study examined the effect of intra-VTA injections of the opioid antagonist NTX on DAMGO- induced feeding in the PVN, and the effect of intra-PVN injections of NTX on DAMGO-induced feeding in the 0006-8993/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2003.08.020 * Corresponding author. Tel.: +44-2890-366580; fax: +44-2890- 368251. E-mail address: e.kim@ulst.ac.uk (E.-M. Kim). www.elsevier.com/locate/brainres Brain Research 991 (2003) 206 – 211