Cristine L Czachowski1, Michael J Delory, Jason D Pope. 1. Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. cczachow@iupui.edu
Abstract
BACKGROUND: The ventral tegmental area (VTA) is a pivotal relay site within the reinforcement circuit that has been shown to play a role in ethanol (EtOH)-motivated behaviors. The primary dopamine projections within this system originate in the VTA and innervate several areas including the nucleus accumbens (NAc) and prefrontal cortex (PFC), and the PFC has afferent glutamate projections to the VTA and the NAc. The following studies utilized 2 different operant paradigms, one focusing on reinforcer-seeking and the other on reinforcer drinking (both with an EtOH and a sucrose reinforcer solution), to elucidate regulation of these behaviors by the posterior VTA, and the specific roles of dopamine and glutamate in this region. METHODS: The present experiments assessed the effects of microinjections of the glutamate (AMPA/kainate) antagonist CNQX and the dopamine D1-like antagonist SCH23390 in the posterior VTA, as well as transient chemical inactivation of this region using tetrodotoxin (TTX). In 4 separate experiments (2 dopamine, 2 glutamate, both with TTX), male Long Evans rats were trained to complete a single response requirement that resulted in access to 10% EtOH or 2% sucrose for a 20-minute drinking period. RESULTS: Prior to microinjections, EtOH-reinforced subjects were consuming approximately 0.45 to 0.65 g/kg EtOH and making approximately 50 responses during intermittent nonreinforced artificial cerebrospinal fluid sessions (Sucrose groups had similar baseline response levels). Overall, TTX inactivation of the VTA consistently decreased reinforcer-seeking but not intake in all experiments. CNQX also dose-dependently decreased EtOH-seeking, with no significant effect on sucrose-seeking or reinforcer intake. SCH23390 had no significant effects on reinforcer-seeking, and very moderately decreased intake of both EtOH and sucrose. CONCLUSIONS: Inactivation of the posterior VTA implicated this region in reinforcer-seeking as opposed to reinforcer intake. Overall, the present findings provide support for the importance of posterior VTA glutamate activity specifically in EtOH-seeking behavior in animals consuming pharmacologically relevant amounts of EtOH.
BACKGROUND: The ventral tegmental area (VTA) is a pivotal relay site within the reinforcement circuit that has been shown to play a role in ethanol (EtOH)-motivated behaviors. The primary dopamine projections within this system originate in the VTA and innervate several areas including the nucleus accumbens (NAc) and prefrontal cortex (PFC), and the PFC has afferent glutamate projections to the VTA and the NAc. The following studies utilized 2 different operant paradigms, one focusing on reinforcer-seeking and the other on reinforcer drinking (both with an EtOH and a sucrose reinforcer solution), to elucidate regulation of these behaviors by the posterior VTA, and the specific roles of dopamine and glutamate in this region. METHODS: The present experiments assessed the effects of microinjections of the glutamate (AMPA/kainate) antagonist CNQX and the dopamine D1-like antagonist SCH23390 in the posterior VTA, as well as transient chemical inactivation of this region using tetrodotoxin (TTX). In 4 separate experiments (2 dopamine, 2 glutamate, both with TTX), male Long Evans rats were trained to complete a single response requirement that resulted in access to 10% EtOH or 2% sucrose for a 20-minute drinking period. RESULTS: Prior to microinjections, EtOH-reinforced subjects were consuming approximately 0.45 to 0.65 g/kg EtOH and making approximately 50 responses during intermittent nonreinforced artificial cerebrospinal fluid sessions (Sucrose groups had similar baseline response levels). Overall, TTX inactivation of the VTA consistently decreased reinforcer-seeking but not intake in all experiments. CNQX also dose-dependently decreased EtOH-seeking, with no significant effect on sucrose-seeking or reinforcer intake. SCH23390 had no significant effects on reinforcer-seeking, and very moderately decreased intake of both EtOH and sucrose. CONCLUSIONS: Inactivation of the posterior VTA implicated this region in reinforcer-seeking as opposed to reinforcer intake. Overall, the present findings provide support for the importance of posterior VTA glutamate activity specifically in EtOH-seeking behavior in animals consuming pharmacologically relevant amounts of EtOH.
Authors: Aqilah M McCane; Curtis D Auterson; Michael J DeLory; Christopher C Lapish; Cristine L Czachowski Journal: Alcohol Date: 2021-01-16 Impact factor: 2.405
Authors: Rusty W Nall; Jasper A Heinsbroek; Todd B Nentwig; Peter W Kalivas; Ana-Clara Bobadilla Journal: J Neurochem Date: 2021-02-13 Impact factor: 5.546