Request Expert

Aggressive behaviour in mice.

Expert's research concerning the neurotransmitter serotonin (5-HT) has delineated a role of for the subreceptors 5-HT1A and 5-HT1B in the control of murine agonistic behaviour. These results suggest the important potential of 5-HT1A agents for the control of anxiety and agonistic behavior.

Considerable controversy still exists concerning the role of 5-HT1A receptors in murine aggression. Our data corroborate some, but not all, previous reports for the role of these sites in aggression. Expert will also examine the role of 5-HT2 5-HT3 and 5-HT4 receptors in murine social and agonistic behaviour, since disagreement centres on whether 5-HT1B or 5-HT2 or 5-HT3 or 5-HT4 receptors influence aggression via an anxiogenic effect.

Closed Head Injury patients and aggression.

Part of the data collection for this work will be undertaken by a current PhD student. This project is based upon the established relationship between aspects of brain function and aggression and will focus on the assessment of this behaviour pre and post trauma.

The pre-morbid personality of brain-injured individuals is a variable that has received limited study in relation to post-morbid aggression. Importantly, studies have often found that relatives of the brain-injured patient report that he/she has undergone a 'personality change' after the injury and that these individuals show an increase in threats of violence. However, some studies indicate that this shift to aggression is not an unavoidable consequence of brain injury but depends very much upon the individual’s pre-morbid personality. Hence brain injury may simply exacerbate a pre-existing proclivity towards aggressive behaviour. The paucity of experimentation examining this variable, however, prohibits any firm conclusions from being drawn. This study attempts to assess how brain-injured individuals' pre-morbid aggressive behaviour is linked to their post-morbid aggression, by employing retrospective ratings from their relatives.

Serotonergic receptors and animal models of anxiety – the elevated zero maze. Interest in the role of 5-HT2 in anxiety developed during the mid-1980s and although numerous pre-clinical studies that have been carried out since, the role of this sub-receptor in anxiety remains to be elucidated. His current experiments have examined the effects of the 5-HT2C agonist and antagonist MK-212 and RS 102221 in the elevated zero-maze model of anxiety. While, in line with previous research, the results with MK-212 may have been interpreted to suggest that 5-HT2C agonism is associated with sedation, closer examination of the data suggested a profile indicative of anxiogenesis. In relation to RS 102221, results suggested that, while the lower doses of this drug resulted in motor disturbance (perhaps due to the non-selective nature of this drug), the higher dose of this drug resulted in anxiolysis. He and postgraduate students propose to continue to use this animal model of anxiety to determine the role of 5-HT3 and 5-HT4 receptors in this behaviour.

Psychosis - Latent Inhibition (LI) in rats.

Expert has developed a paradigm which employs latent inhibition in the rat as an animal model of psychosis. This work was performed Department of Therapeutics and Pharmacology, QUB, and two PhD students demanded considerable effort in producing computer software to monitor stimuli and record the animals’ behavioural responses. The purpose of this research is to use the model of latent inhibition in the rat to assess the potential clinical efficacy of new compounds developed as neuroleptic agents. To-date, he and another professor have tested the effects of proven neuroleptic compounds such as haloperidol, clozapine and remoxipride which demonstrate an enhancement of LI. The data obtained for atypical neuroleptics, such as clozapine, demonstrates the robustness of the LI model in that this paradigm can detect neuroleptic-like actions that result from manipulations of neurotransmitters other than dopamine. Expert and the professor are now proceeding to evaluate the influences of novel compounds on LI with a view to assessing potential clinical applications. Funds received from Zeneca (£15,000) will be used towards this research.

Psychosis - Latent Inhibition (LI) in healthy volunteers / schizophrenic patients.

Expert based on our animal work, to assess LI in healthy volunteers and schizophrenics. Preliminary data with the antipsychotic agent chlorpromazine indicate a successful demonstration of the compound’s enhancement of LI in healthy volunteers; a result consistent with our animal data. This paradigm will be used in conjunction with other psychological (CANTAB software) and physiological (eye movement tests) to assess the onset/treatment of schizophrenia.

He has two PhD students working on this project and have submitted applications to funding bodies seeking financial support for this research concerning LI in rats and LI in healthy volunteers.

Expert was invited by researchers in America and Europe to collaborate on a meta-analysis of findings for the relationship between serotonin and aggression. This work resulted in a substantial paper accepted by the prestigious journal Psychological Bulletin for publication (see Selected Publications section).Within Queen’s University Belfast, he was invited to collaborate on research concerning mood and bipolar disorder. Expert researched concerns with patients who had suffered traumatic brain injuries.