Studies on neural mechanisms underlying emotions : experiments with pharmaceutical and physiological stimuli on behavior and brain signals in rodents and non-human primates

This thesis investigated aspects of emotion processing in two animal species, the rat and the monkey (Macaca mulatta). Studies in rats (Studies I and II) aimed at elucidating whether paracetamol, a widely used pain-killer and fever-reducing medication, might also affect the animal’s mood, as suggested by some studies in humans. The studies in monkeys (Studies III and IV) aimed at investigating the neural basis of emotion in the amygdala and orbitofrontal cortex (OFC) during auditory emotion processing. A peripheral nerve injury-induced neuropathy has been associated with affective pain and disorders such as anxiety and depression. The spared-nerve injury (SNI) is an animal model of chronic neuropathy. Using the rat model of SNI, Study I investigated the development of mechanical hypersensitivity following nerve injury in animals treated with an antagonist of the transient receptor potential ankyrin 1 (TRPA1) channel that is putatively involved in mediating the paracetamol-induced actions. SNI produced marked hypersensitivity which was attenuated by block of the spinal TRPA1 channels. Paracetamol is a common medication that is used to alleviate pain and reduce fever. Besides its antinociceptive and fever-reducing effects, paracetamol has been suggested to affect various cognitive functions such as motivation, and to reduce discomfort related to decision making and empathy for pain. Study II investigated effects of paracetamol on anxiety, mood, activity and memory in healthy rats and in rats with SNI. The results showed that, in healthy rats, a high dose of paracetamol produced anxiety-like and anhedonic behavior, and impaired recognition memory. In neuropathic rats, a low dose of paracetamol reduced anxiety probably by reducing neuropathic pain. Prepulse inhibition (PPI) refers to a decreased reaction of an organism to a stimulus when another weaker stimulus precedes it. Using the local field potentials (LFPs) recording technique and a PPI paradigm, Study III explored the cortical responses in the monkey caudolateral belt of the superior temporal gyrus (STGcb) to simple auditory stimulation in two conditions; when the monkey was alone, and when another monkey was in the same room drawing attention away from the auditory stimuli. The LFPs to an auditory Pulse stimulus were significantly suppressed by an auditory Prepulse stimulus. The PPI of LFPs was not affected by distraction produced by the presence of a conspecific. These results demonstrate the PPI in the monkey STGcb and suggest that the PPI of auditory cortical responses in the monkey STGcb is an inhibitory process that is independent of conscious attention. Both the amygdala and the orbital frontal cortex (OFC) are key components of the central circuitry underlying emotion processing. Neural underpinnings of emotion processing have been extensively studied using visual stimuli but much less using auditory stimulation. In Study IV, LFPs were recorded in the amygdala, OFC and two control cortical areas, STGcb and V1 to investigate whether oscillatory activity in these areas reflects the valence of the auditory stimuli. Four types of monkey vocalizations (neutral, happy, fearful, threatening) were used as stimuli. The results showed that the amygdala and the OFC have a role in the processing of emotionally salient, naturalistic auditory stimuli. The functional interactions in the amygdala–OFC axis were distinct to the different emotional valences suggesting that the functional coherence between amygdala and OFC contributes to the emotion-associated behavior. In conclusion, this thesis applied behavioral testing, pharmacological manipulations and electrophysiological recordings in animal experiments, and focused on questions that have relevance in understanding human emotion processing. The thesis showed that even in rats, the widely used fever and pain medicine paracetamol affected their behavior in tests that measured anxiety, anhedonia and memory, warranting further investigation of the effects of widely used analgesics on cognition. The thesis also elucidated neural mechanisms of the understudied auditory emotion processing and showed that the basolateral nucleus of the amygdala and the OFC have a role in the processing of emotionally valenced auditory information.