Haloperidol-induced emotional defecation: a possible model for neuroleptic anxiety syndrome

Abstract

The neuroleptic haloperidol was found to produce increased defecation in laboratory rats when tested in well habituated environments. It is well known that haloperidol induces catalepsy through antagonism of striatal dopaminergic receptor mechanisms. When another cataleptic agent, morphine, was tested, no significant increases in defectation were detected. Another study focused on the possible role of peripheral dopamine receptor sites within the gastrointestinal tract on neuroleptic-induced defecation. When the peripheral dopamine receptor antagonist domperidone was tested, no significant differences in fecal elimination were recorded. Thus, it appeared that the cataleptic state per se, or the peripheral effects of haloperidol did not seem to be responsible for the increased defecation. Defection is often used as an index of emotionality. The fact that this measure increased following administration of a major tranquilizer suggested the need to study more directly the relationship of this phenomenon of defecation with the affective state of the animal. In a control study it was found that the antianxiety agent benzodiazepam did not by itself influence defecation. However, those animals which were pre-injected with diazepam followed by haloperidol did not show increased defecation. Thus under certain circumstances, normal rats given haloperidol show "emotional defecation" which seems to reflect increased anxiety. This finding may serve as a basis for the development of an animal model for some of the atypical side effects of major tranquilizers, such as akathisia, dysphoria, and neuroleptic anxiety syndrome.

Subjective Response to Neuroleptics in Schizophrenia

“…Recently, a rat model that used increased defecation as an index of emotionality has been proposed to study side effects of neuroleptics (Sanberg et al 1989). Russell et al (1987 a ) has reported that HPL and pimozide decreased emotional defecation in rats when tested in a novel environment, but the same drugs increased emotional defecation when the animals were tested in their habituated environment (Russell et al 1987 b ). These paradoxical effects suggest that the response to neuroleptics could be dependent on the emotional state of the organism and may be analogous to the dysphoria some individuals experience during neuroleptic treatment.…”

Neuroleptic Dysphoria: In Search of an Animal Model

“…Hall (1934) first reported that defecation levels increase when the rat is placed in a novel or arousing situation. When pre-treated with haloperidol or pimizide there is, as might be expected, a decrease in emotional defecation when measured in a novel environment (Russell et al, 1987a). However, with the same pre-treatment there is an increase in the level of defecation when placed in the home, or a habituated, environment (Russell et al, 1987b).…”

“…But, neither mechanism explains the akathesia, rigidity, anxiety, agitation, and panic which can accompany neuroleptic administration. While the mechanism has not been elucidated, the constellation of symptoms of akathesia, rigidity, affective disturbances, and coarse tremor are now recognized as the "Neuroleptic Syndrome" (Freyhan, 1980), or "Neuroleptic-Separation Anxiety Syndrome" (Russell, Hagenmeyer-Houser and Sanberg, 1987a).…”

Die initial dysphorische Reaktion (IDR) auf die Ersteinnahme von Neuroleptika

“…Zudem berichten 2 Studien von einer Verminderung der Dysphorie im Verlauf durch Dosisreduktion [8,9]. Giardini, Sanberg und Russel [13,35,36,37] kamen nach Tierversuchen an Ratten zu der Hypothese,dass Umweltbedingungen,beispielsweise vertraute vs.nichtvertraute Umweltbedingungen, die aversive Reaktion auf eine Erstgabe von Chlorpromazin modulierten. Für die menschliche dysphorische Reaktion ist der Einfluss von Umweltbedingungen (z.B.auch der Arzt-Patient-Beziehung) bislang nicht untersucht worden.…”