Samenvatting

Nicotine is a well-known and highly addictive substance with complex effects on cognition, anxiety, and neurophysiology. Despite its short-term anxiolytic effects, this drug often exacerbates anxiety symptoms. It disrupts emotional regulation through its impact on the central nucleus of the amygdala (CeA) – a key brain region for stress and sensory processing that is susceptible to drug-related stimuli. The nicotinic acetylcholine receptors (nAChRs) of the cholinergic system play a crucial role in nicotine addiction, enhancing synaptic plasticity by promoting neurotransmitter release and supporting long-term memory formation. Different receptor subtypes have distinct effects, and this study aims to investigate the role of the a4b2 nACh receptors and their co-localisation with stress-regulating neuropeptide Y (NPY) neurons within the CeA, focusing on their potential involvement in neuronal morphology, synaptic plasticity, and social behavioural changes. Analysis of fluorescent in situ hybridisation (FISH) images confirmed co-localisation of NPY and a4b2 nAChR markers, suggesting potential interconnected involvement in various neuronal pathways. After determining the correct coordinates for the CeA during stereotaxic surgeries, CaMKII-Cre-GFP and CMV-Cre-GFP viruses were injected into both TOM and ChAT/TOM mice to reveal the potential presence of spiny neuronal populations. The method was validated for use, but the signals expressed high background noise, which limited the structural analysis of neuronal morphology. In contrast, NPY-Cre mice showed more specific labelling, though dendritic spine density remained low compared to cortical pyramidal neurons. Thus, the neuronal population in the CeA does not exhibit enough spines to serve as a proxy to interrogate synaptic plasticity, so other technological approaches need to be implemented to search for such activity. Because the CeA plays a role in the control of social behaviour, the effects of acute nicotine administration were tested in this behavioural domain. Acute nicotine injections (0.5 mg/kg) consistently reduced social interaction time in mice across tests (Three Chamber Test, Social Interaction Test, MEGIT, and Resident-Intruder Test), without impairing locomotion, social preference, or
social memory. These findings suggest that nicotine does not affect social behaviour and social motivation, but it reduces overall social interaction and explorative tendencies. While the CeA may not be the primary site for nicotine-driven spine-specific synaptic plasticity affecting
behaviour, the results showcase the importance of ongoing investigation into nicotine’s influence on neural circuits, emotional processing, and behavioural mechanisms.