Alpha 1 -adrenergic receptor blockade in the VTA modulates fear memories and stress responses Wojciech B. Solecki a,b,n , Klaudia Szklarczyk a , Kamil Pradel b , Grzegorz Dobrzański b , Ryszard Przewłocki b a Department of Neurobiology and Neuropsychology, Institute of Applied Psychology, Jagiellonian University, 4 Lojasiewicza Street, 30-348 Krakow, Poland b Department of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland Received 14 July 2016; received in revised form 14 April 2017; accepted 22 May 2017 KEYWORDS Noradrenaline; Ventral tegmental area; Alpha 1 -adrenergic receptor; Prazosin; Fear memory Abstract Activity of the ventral tegmental area (VTA) and its terminals has been implicated in the Pavlovian associative learning of both stressful and rewarding stimuli. However, the role of the VTA noradrenergic signaling in fear responses remains unclear. We aimed to examine how alpha 1 -adrenergic receptor (α 1 -AR) signaling in the VTA affects conditioned fear. The role of α 1 - AR was assessed using the micro-infusions into the VTA of the selective antagonists (0.1–1 mg/ 0.5 ml prazosin and 1 mg/0.5 ml terazosin) in acquisition and expression of fear memory. In addition, we performed control experiments with α 1 -AR blockade in the mammillary bodies (MB) – a brain region with α 1 -AR expression adjacent to the VTA. Intra-VTA but not intra-MB α 1 - AR blockade prevented formation and retrieval of fear memories. Importantly, local adminis- tration of α 1 -AR antagonists did not influence footshock sensitivity, locomotion or anxiety-like behaviors. Similarly, α 1 -AR blockade in the VTA had no effects on negative affect measured as number of 22 kHz ultrasonic vocalizations during fear conditioning training. We propose that noradrenergic signaling in the VTA via α 1 -AR regulates formation and retrieval of fear memories but not other behavioral responses to stressful environmental stimuli. It enhances the encoding of environmental stimuli by the VTA to form and retrieve conditioned fear memories and to predict future behavioral outcomes. Our results provide novel insight into the role of the VTA α 1 -AR signaling in the regulation of stress responsiveness and fear memory. & 2017 Elsevier B.V. and ECNP. All rights reserved. www.elsevier.com/locate/euroneuro http://dx.doi.org/10.1016/j.euroneuro.2017.05.008 0924-977X/& 2017 Elsevier B.V. and ECNP. All rights reserved. n Correspondence to: Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland. Fax: + 48 12 637 45 00. E-mail address: wsolecki@if-pan.krakow.pl (W.B. Solecki). European Neuropsychopharmacology (]]]]) ], ]]]–]]] Please cite this article as: Solecki, W.B., et al., Alpha 1 -adrenergic receptor blockade in the VTA modulates fear memories and stress responses. European Neuropsychopharmacology (2017), http://dx.doi.org/10.1016/j.euroneuro.2017.05.008