Modulation of Brain Stimulation Reward by GABA in the Ventromedial Nucleus of the Thalamus Open Access

Piryani, Manisha (Spring 2018)

Permanent URL: https://etd.library.emory.edu/concern/etds/9w032300g?locale=en
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Abstract

 

Abstract

Modulation of Brain Stimulation Reward by GABA in the Ventromedial Nucleus of the Thalamus

By Manisha Piryani

The reward system has generated a lot of interest in the field of neurobiology, specifically in regards to the mesolimbic dopamine system. While several studies hold the dopaminergic effect at the nucleus accumbens accountable for inducing the rewarding effect, the present study attempts to see where this “reward signal” goes after the accumbens. The objective of the study was to use the autotitration paradigm and to manipulate GABAergic effects in the ventromedial nucleus of the thalamus (VMT) in order to determine the role of the VMT in intracranial self-stimulation (ICSS) reward. In the following study, the GABAergic input to the VMT, which comes particularly from the substantia nigra pars reticulata (SNPR), was manipulated in a sample of eight rats through the intra-VMT injection of GABA antagonist picrotoxin and GABA agonist muscimol. The behavioral effects of the drugs were shown through their activity in autotitration ICSS. After injection of picrotoxin in the VMT, the rats showed vigorous motoric ability, but decreased ICSS responding and showed “earlier” resetting of the mean intensity, a behavioral pattern described as “decreased reward” in the theoretical autotitration ICSS scheme of Neill et al. (1982). Following muscimol injection, the locomotor activity of the rats decreased, and decreased ICSS responding was accompanied by “later” resetting, a behavioral pattern described as “decreased effort” by Neill et al. (1982). These results suggest an important involvement of GABA in the brain reward system.

Keywords: autotitration, intracranial self-stimulation, reward, nigrothalamic pathway, ventromedial nucleus of the thalamus

 

Table of Contents

 

Introduction…………………………………………………………………………………………………………1

ICSS and Anatomy………………………………………………………………………………………………1

Dopamine and Reward…………………………………………………………………………………………2

Ventromedial Nucleus of the Thalamus………………………………………………………………4

The Autotitration Procedure…………………………………………………………………………………7

Interpretation of Results………………………………………………………………………………………8

Purpose and Hypothesis………………………………………………………………………………………9

 

Materials and Methods…………………………………………………………………………………………9          

Animals…………………………………………………………………………………………………………….…9    

Surgery………………………………………………………………………………………………………………10

Device Implantation and Coordinates………………………………………………………………11

Post-Operative Care…………………………………………………………………………………………11

ICSS Testing……………………………………………………………………………………………………12

Autotitration……………………………………………………………………………………………………12

Microinjections…………………………………………………………………………………………………13

Analysis of Results……………………….…………………………..…………………………………14

 

Results………………………………………………………………………………………………..…………14

ICSS Responding Following Picrotoxin…………………………………………………..……15

Mean Reset Intensity in Picrotoxin………………………………………………………………15

ICSS Responding in Muscimol………………………………………………………………………15

Mean Reset Intensity in Muscimol ………………………………………………………………15

Observation of Rat Behavior after Picrotoxin………………………………………………16

Observation of Rat Behavior after Muscimol…………………………………………………16

Histology…………………………………………………………………………………………………………17

Discussion………………………………………………………………………………………………………17

Behavioral Interpretation of Picrotoxin Results……………………………………………17

Neural Interpretation of Picrotoxin Results……..……………………………………………19

Behavioral Interpretation of Muscimol Results………………………………………………20

Neural Interpretation of Muscimol Results……………………………………………………21

Comparison to Williams and Herberg (1986) ………………………………………………22

Limitations………………………………………………………………………………………………………23

Implications and Future Directions…………………………………………………………………23

 

References ………………………………………………………………………………………………………26

 

Figure 1. Lateral view of accumbens route to cortex..……………………………………31

Figure 2. Change in average ICSS responding as a function of picrotoxin ....32

Figure 3. Change in mean reset intensity as a function of picrotoxin. …………33

Figure 4. Change in total ICSS responding as a function of muscimol. …………34

Figure 5. Change in mean reset intensity as a function of muscimol………………35

Figure 6. Placement of cannulae and electrode……………………..…………………………36

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