Glutamate receptors in the ventral tegmental area: a potential mechanism involved in long term potentiation
Degree GrantorUniversity of Canterbury
Degree NameMaster of Science
In the present study, footshock, which produces a powerful aversive emotional response was used in a Pavlovian conditioning experiment as an unconditioned stimulis (UCS), and was paired with the presentation of a light used as a conditioned stimulis (CS). There is an accumulation of evidence that supports the assertion that dopaminergic (DA) neurons within the ventral tegmental area (VTA) are active in processes that contribute to the amygdala-based circuitry involved in regulating emotionally salient responses. To build upon findings implicating VTA DA, excitatory glutamate (Glu), NMDA and AMPA receptors, were examined with respect to their role in Pavlovian conditioned fear responding. Fear potentiated startle (FPS) was used to assess the effects of intra-VTA infused AP5, and intra-VTA infused CNQX on conditioned fear responding in laboratory rats. The administration of the NMDA receptor antagonist AP5 (at 1.0, 2.5, and 5.0ug doses), blocked the ability of a conditioned stimulus (CS) previously paired with footshock to become conditioned to the UCS. Similarly, administration of the AMPA receptor antagonist CNQX (at 1.0, 2.5, 5.0ug doses), inhibited the ability of the CS to become conditioned to the UCS. The results of this study indicate the VTA is an important site for synaptic modifications associated with fear learning, and that activation of excitatory Glutamatergic receptors in the VTA play a necessary part of the processing underlying fear conditioning. Measures of shock reactivity demonstrated that the infusion of AP5 and CNQX into the VTA did not inhibit baseline startle amplitudes. The administration of AP5 and CNQX did not suppress the perception of footshock as an aversive stimulus. This study provides further definition to established knowledge surrounding the neural processes whereby neutral environmental cues gain negative emotional salience as occurs in fear conditioning. It was hypothesised that the action of excitatory glutamatergic transmission within the VTA acts on NMDA and AMPA receptors is to assist in the acquisition of Pavlovian conditioned fear, possibly through the same synaptic mechanisms that govern LTP.