5HT drugs in animal models of anxiety

Abstract

It has been widely accepted that 5HT neurones promote anxiety, in humans as well as in animal models. This could be termed the "classic" hypothesis and it has led to a determined search for drugs which reduce 5HT function, especially agents which have selective actions at 5HT receptor subtypes. However, these novel agents tend to have weak and/or variable effects in animal models and more detailed examination of their actions suggests that not all findings are accounted for by the classic hypothesis. There appear to be circumstances in which increased 5HT activity can reduce anxious behaviour. There is increasing evidence for multiple anxiety mechanisms, which may be able to explain differential patterns of drug effects within and between models. Animal models of anxiety may also detect non-anxiety factors: effects on cognition or on impulsivity could be reflected in some models. This could be important in the light of recent evidence that 5HT-selective reuptake inhibitors are effective in impulsivity disorders. The classic hypothesis of 5HT function in anxiety may be only one part of an increasingly complex story. Unravelling the rest of this story is likely to lead to new insights in our understanding of anxiety and related disorders.

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

“…Thus, it is perhaps not surprising that chronic SCIT treatment did not prevent the CUS-induced increase in anxiety-like behavior on the plus-maze in the present study, nor that SCIT treatment alone had a modest anxiogenic effect. As SSRIs are clearly effective in treating human anxiety, one obvious implication from this literature, as well as the present study, is that many commonly used assays of anxiety-like behavior in rats are not valid models of human anxiety disorders that are responsive to SSRI treatment (eg, see Handley, 1995;Handley and McBlane, 1993).…”

“…A more subtle interpretation, however, is that the anxiolytic effects of chronic SSRI treatment may in fact be attributable more to their effects on cognitive or perceptual processes that might lead to a disproportionate or inappropriate subjective feeling of distress and anxiety in the absence of an appropriately threatening stimulus (see Beck, 1976;Coles and Heimberg, 2002;Mathews and Mackintosh, 1998), rather than any effect they may exert on the presumably appropriate and adaptive behavioral responses to acute stressors that are measured in most animal models of 'anxiety' (Handley and McBlane, 1993). It would thus be useful to be able to adopt an animal model of anxiety in which the behavioral response was not adaptive (as it is in such models as the elevated plus-maze, defensive burying or social interaction tests), but rather was seen as pathological and inappropriate to the context.…”

Serotonin Reuptake Inhibition by Citalopram in Rat Strains Differing for Their Emotionality

“…On acute administration to rodents, SSRIs display anxiogenic (Chopin and Briley 1987;Handley and McBlane 1993;Griebel et al 1994), anxiolytic (Jackson et al 1995;Sanchez 1995;Schreiber et al 1998), or no effects at all The animals were treated with 0.9% NaCl or citalopram 1 h before sacrifice. Data are the mean Ϯ SEM values of 4 rats/treatment/strain.…”

Envolvimento dos receptores 5-HT2 da amígdala nos níveis de ansiedade induzidos pela exposição de ratos ao labirinto em cruz elevado

“…Por exemplo, antagonistas dos subtipos 5-HT 2 (como a ritanserina e a ketanserina) e 5-HT 3 (como o ondansetrom, o zacopride e o BRL 46470) promovem efeitos ansiolíticos em vários modelos animais (para revisões, ver Cruz & cols., 1995Cruz & cols., , 1997Handley & McBlane, 1993) e em ensaios clínicos com humanos (para revisões, ver Graeff & cols., 1996;McNair & cols., 1982). Estudos neuroquímicos também indicam que a buspirona, primeiro ansiolítico seletivo de ação serotonérgica introduzido na clínica médica (Ninan & cols., 1998), atua preferencialmente em nível dos auto-receptores 5-HT 1A nos núcleos da rafe (Hoyer & Martin, 1997).…”