Trudy A Green1, Sarah J Baracz1,2, Nick A Everett1, Katherine J Robinson3, Jennifer L Cornish4,5. 1. Department of Psychology, Macquarie University, Sydney, NSW, 2109, Australia. 2. Centre for Emotional Health, Macquarie University, Sydney, NSW, 2109, Australia. 3. Department of Biomedical Sciences, Macquarie University, Sydney, NSW, 2109, Australia. 4. Department of Psychology, Macquarie University, Sydney, NSW, 2109, Australia. Jennifer.cornish@mq.edu.au. 5. Centre for Emotional Health, Macquarie University, Sydney, NSW, 2109, Australia. Jennifer.cornish@mq.edu.au.
Abstract
RATIONALE: The development of effective anxiety treatments has been hindered by limited understanding of the neurobiological mechanisms involved in anxiety regulation. Whilst gamma-aminobutyric acid (GABA) neurotransmission in the prefrontal cortex (PFC) is one mechanism consistently implicated in anxiety regulation, PFC subregions may contribute uniquely. OBJECTIVES: The present study examined the effects of inactivating the PFC subregions of the prelimbic cortex (PrL) or orbitofrontal cortex (OFC) through GABAA receptor (GABAAR) activation, on anxiety behaviours in male Wistar rats. METHODS: Sixty-six male Wistar rats were surgically implanted with bilateral cannulae into the PrL (n = 33) or the OFC (n = 33). Rats then received a microinjection of either the GABAA receptor agonist muscimol or vehicle prior to each experiment, conducted 1 week apart. Measures of anxiety were examined using the elevated plus maze (EPM) and the emergence test (ET). The effect on locomotor activity (baseline or methamphetamine-induced) was also tested. RESULTS: Differential effects of brain region inactivation on anxiety-like behaviour were shown by measures in the EPM and ET; muscimol infused into the PrL-reduced anxiety-like behaviour, yet had no significant effect when infused into the OFC, compared with control treated rats. No effects on locomotor activity at baseline or following methamphetamine treatment were found. CONCLUSIONS: This study highlights that activation of GABAARs specifically within the PrL, but not OFC, reduces anxiety behaviours in male rats. This suggests that activity of the PrL plays a more important role than the OFC in the neurobiological mechanisms of unconditioned anxiety and should be targeted for future therapies.
RATIONALE: The development of effective anxiety treatments has been hindered by limited understanding of the neurobiological mechanisms involved in anxiety regulation. Whilst gamma-aminobutyric acid (GABA) neurotransmission in the prefrontal cortex (PFC) is one mechanism consistently implicated in anxiety regulation, PFC subregions may contribute uniquely. OBJECTIVES: The present study examined the effects of inactivating the PFC subregions of the prelimbic cortex (PrL) or orbitofrontal cortex (OFC) through GABAA receptor (GABAAR) activation, on anxiety behaviours in male Wistar rats. METHODS: Sixty-six male Wistar rats were surgically implanted with bilateral cannulae into the PrL (n = 33) or the OFC (n = 33). Rats then received a microinjection of either the GABAA receptor agonist muscimol or vehicle prior to each experiment, conducted 1 week apart. Measures of anxiety were examined using the elevated plus maze (EPM) and the emergence test (ET). The effect on locomotor activity (baseline or methamphetamine-induced) was also tested. RESULTS: Differential effects of brain region inactivation on anxiety-like behaviour were shown by measures in the EPM and ET; muscimol infused into the PrL-reduced anxiety-like behaviour, yet had no significant effect when infused into the OFC, compared with control treated rats. No effects on locomotor activity at baseline or following methamphetamine treatment were found. CONCLUSIONS: This study highlights that activation of GABAARs specifically within the PrL, but not OFC, reduces anxiety behaviours in male rats. This suggests that activity of the PrL plays a more important role than the OFC in the neurobiological mechanisms of unconditioned anxiety and should be targeted for future therapies.
Authors: Rawan AlSubaie; Karyna Mishchanchuk; Candela Sánchez-Bellot; Ryan W S Wee; Andrew F MacAskill Journal: Nat Commun Date: 2022-01-17 Impact factor: 17.694