1. ¹Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
2. ²Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
3. ³CREST, Japan Science and Technology Agency, Saitama, Japan

Correspondence: Dr M Sekiguchi, Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. Tel: +81 42 346 1715; Fax: +81 42 346 1745; E-mails: elec1@ncnp.go.jp or sekiguch@ncnp.go.jp

⁴Current address: Department of Neuroscience, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA

Received 20 July 2007; Revised 25 January 2008; Accepted 15 February 2008; Published online 19 March 2008.

Abstract

Neurotensin receptor type-1 (Ntsr1) is the main receptor subtype that underlies neurotensin (NT)-mediated modulation of the dopamine (DA) system. Although NT and DA coexist in the basolateral nucleus of the amygdala (BLA), the function of Ntsr1 in the amygdala is not well characterized. In the present study, we utilized Ntsr1 knockout (Ntsr1-KO) mice to examine the role of Ntsr1 in the amygdala. In acute brain slices of Ntsr1-KO mice, synaptic currents elicited in BLA pyramidal neurons by electrical stimulation of the lateral nucleus of the amygdala (LA) were greatly potentiated by tetanic stimulation (BLA-long-term potentiation (LTP)). Such potentiation was not evident in pyramidal neurons of wild-type mice. In the presence of an antagonist of Ntsr1, SR48692, BLA-LTP was consistently observed in the neurons of wild-type mice, suggesting that both inherited deletion and acute pharmacological blockade of Ntsr1 induce BLA-LTP. BLA-LTP in Ntsr1-KO mice was impaired by sulpiride, a DA D₂-like receptor antagonist. Conversely, quinpirole, a D₂-like receptor agonist, induced pronounced BLA-LTP in wild-type mice, suggesting the upregulation of D₂-like receptor activity in Ntsr1-KO mice. The ratio of NMDA receptor-mediated to non-NMDA receptor-mediated synaptic currents in Ntsr1-KO mouse BLA neurons was approximately double that measured in wild-type mouse neurons. Furthermore, quinpirole potentiated NMDA receptor-mediated synaptic currents in the BLA of wild-type mice. These results suggest that, without Ntsr1, synaptic responses from the LA to BLA pyramidal neurons undergo LTP in response to tetanus stimulation through facilitation of D₂-like receptor-induced activation of NMDA receptors.