Dopamine containing neurons in the ventral tegmental area : a potential site of action for benzodiazepine anxiolytics

Abstract

Footshock is a strong aversive environmental stimulus often used as the unconditioned stimulus (UCS) in Pavlovian fear conditioning experiments. In the present study, the relationship between VTA dopamine (DA) neurons, y­ Aminobutyric acidA (GABAA) and benzodiazepine receptors in governing the fear-arousing properties of footshock was evaluated. Using the shock sensitisation of acoustic startle amplitudes as a behavioral indicator of fear, the present study demonstrates that intraVTA infusion of the somatodendri tic D 2 receptor agonist quinpirole ( 0. 7 5, 1. 5 and 3,0 µg) dose dependently blocked fear arousal, presumably due to inhibition of DA neural activity. Similarly, intraVTA infusion of the GABAA receptor agonist muscimol (0.5 and 1.0 µg) and the full benzodiazepine receptor agonist flurazepam (60.0 and 120.0 µg) suppressed footshock-induced emotional responding. None of the drugs infused directly into the VTA depressed baseline acoustic startle amplitudes or diminished the perceived aversive effects of footshock as measured by shock reactivity. The present results further refine the known neural dynamics of the fear motivational properties of VTA DA neurons. It was hypothesised that the VTA, through its connections to forebrain regions implicated in emotionality, may be an important site for the action of benzodiazepine anxiolytics.