Plenary lecture

Andrew J Lawrence: Peptides and reward-seeking behaviour

On lecturer

Andrew J Lawrence Professor Andrew Lawrence is an NHMRC Principal Research Fellow & Associate Director at the Florey Institute of Neuroscience & Mental Health where he is Head of the Division of Behavioural Neuroscience and runs the Addiction Neuroscience laboratory. Andrew has published over 200 original articles & reviews, and been cited >7500 times. Andrew was Treasurer of the Australian Neuroscience Society (2002–2008) and is a Fellow of the British Pharmacological Society. He was Senior Editor of The British Journal of Pharmacology (2007–2014) and is currently a reviews editor with The British Journal of Pharmacology. He is Deputy Editor in Chief of Pharmacology Research & Perspectives, Associate Editor of both Neurochemical Research and the Journal of Pharmacological Sciences. He sits on the editorial board of Addiction Biology. Andrew was recently President of the Asian-Pacific Society for Neurochemistry (2014–16) and is currently a Council member of the International Society for Neurochemistry.

In his spare time, Andrew is a keen cyclist and a surf life guard.

On lecture: Peptides and reward-seeking behaviour

Relapse and hazardous drinking represent the most difficult clinical problems in treating patients with alcohol use disorders. Stress is a key precipitant of relapse, and relaxin-3 signalling modulates both stress responses and alcohol intake. We therefore examined a role for the relaxin-3 system in alcohol-seeking. In iP rats, icv microinjection of a selective RXFP3 antagonist prevented yohimbine-induced reinstatement of alcohol-seeking, discrete microinjections implicated the dorsal BNST and central amygdala as loci. Relaxin-3 neurons are predominantly located in the pontine nucleus incertus (NI) which is highly sensitive to CRF. Intra-NI microinjection of a selective CRF1 receptor antagonist (CP376395) attenuated yohimbine-induced reinstatement of alcohol-seeking. After long-term voluntary alcohol intake in iP rats, qPCR revealed upregulation of mRNA encoding CRF1 and RXFP3 receptors in NI. We also found CRF within the NI, which was confirmed in rat and CRF-Cre x TdTomato reporter mouse brain. These data suggest NI neurons contribute to reinstatement of alcohol seeking, via an involvement of CRF1 signaling. The NI also receives orexinergic innervation and so we undertook analogous experiments. Bilateral NI injections of the OX2 receptor antagonist TCS-OX2-29 attenuated yohimbine-induced reinstatement of alcohol seeking, while the OX1 receptor antagonist SB-334867 had no effect. Orexin-A depolarized NI neurons recorded in coronal brain slices, sensitive to bath application of TCS-OX2-29, but not SB-334867. These data suggest an excitatory orexinergic input to NI contributes to yohimbine-induced reinstatement of alcohol seeking, predominantly via local OX2 receptor signalling. Collectively, these data implicate CRF and orexin inputs to relaxin-3 neurons of the NI in alcohol-seeking.

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