Serotonergic and steroidal influences on impulsive behaviour in rats

Detta är en avhandling från Uppsala : Acta Universitatis Upsaliensis

Sammanfattning: Impulsiveness is a trait contributing to the personality of all human beings to a greater and lesser extent. In a pathological form it can lead to impulsive behaviour which is an important component of many psychiatric and neurological disorders.In this thesis operant procedures have been developed to isolate and study the influence of impulsivity on the preparation, execution and outcome of behaviour in rats, and measures identified which are proposed to provide a quantitative assessment of this influence. These procedures were an unreliable visual discrimination, a paced fixed consecutive number schedule (paced FCN), and delay of reinforcement, respectively. They were validated by behavioural and motivational manipulations, and by examining the effects of a series standard drugs, amphetamine, haloperidol, chlordiazepoxide, imipramine and ethanol.The effects of receptor-specific serotonergic agonists and antagonists on responding under a paced FCN schedule were then studied. The 5-HT1A agonist, 8-OH-DPAT, increased the average chain length, proposed to reflect a reduction in impulsivity, whereas the 5-HT2 agonist DOI, had the opposite effect. Drugs which had a more general effect of enhancing serotonergic activity, such as the reuptake inhibitor, citalopram, or the serotonin releaser para-chloramphetamine, and the serotonergic antagonists had small or no effects. These results indicate that the role for serotonin in regulating impulsivity is more complex than hitherto suggested.The effects of the androgenic steroid, testosterone, on impulsivity were studied in two experiments. Sub-chronic treatment with supraphysiological doses of testosterone cypionate had no effect on behaviour in either the paced FCN or delay of reinforcement procedures. Spontaneously Hypertensive Rats (SHR), which have a reduced sensitivity to circulating testosterone, showed a behaviour pattern in a paced FCN procedure characterised by mildly elevated impulsivity. These data suggest that testosterone has no effect on appetitively motivated impulsive behaviour.

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