Exploring the Behavioural Effects of Compound-21 Using Novel Object Recognition and Object in Place Tests in Long Evans Rats
Date
2023-10-03
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
0000-0001-9904-5425
Type
Thesis
Degree Level
Masters
Abstract
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) have gained popularity as a tool to investigate the neural substrates of behaviour in rodents. When used with spontaneous behavioural tests of memory in rodents, DREADDs allow for a unique opportunity to advance our understanding of how specific neuronal populations contribute to cognition. While data on the use of DREADDs to study memory with spontaneous tasks in rats is somewhat limited, there is evidence to suggest that the canonical DREADD agonist, clozapine-N-oxide (CNO), exhibits off target effects on recognition memory assessed with the Novel Object Recognition (NOR) test. While newer DREADD agonists are available, an understanding of how these novel compounds impact rat behaviour unspecific to DREADD activation is lacking. Therefore, I sought to test whether the DREADD agonist, Compound 21 (C21), affected recognition memory assessed by NOR or, associative memory assessed by the Object-in-Place (OiP) test. I also investigated whether DREADD-mediated inhibition of parvalbumin (PV+) gamma-amino butyric acid (GABA)ergic interneurons of the medial prefrontal cortex (mPFC) would impair associative memory as measured by OiP. I showed that C21 did not affect either sex in NOR, or females in OiP. Male rats failed to exhibit robust discrimination in OiP following either control or C21 treatment; however, total object exploration times of male rats were not altered by C21. Lastly, PV-Cre rats transfected with an inhibitory DREADD in the mPFC and treated with C21 showed normal exploration of objects in OiP. Poor discrimination in OiP and low vector co-expression of DREADD with mPFC parvalbumin-containing interneurons precluded conclusions about potential impacts of inhibiting these cells on associative memory. While C21 did not impair discrimination of objects in females tested in OiP, further work is needed to replicate this finding in males.
Description
Keywords
DREADD, Recognition Memory
Citation
Degree
Master of Science (M.Sc.)
Department
Anatomy and Cell Biology
Program
Physiology