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Directional Persistence in the Rewarded Alternation Model of Obsessive-compulsive Disorder is Responsive to both Dopaminergic and Serotonergic Manipulations

Published online by Cambridge University Press:  16 April 2020

D. Kontis ,
V. Boulougouris ,
S. Papadopoulos ,
V.-M. Papakosta ,
S. Kalogerakou ,
C. Poulopoulou ,
E. Tsaltas  and
G. Papadimitriou
D. Kontis
Affiliation:
Experimental Psychology Laboratory, Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece
V. Boulougouris
Affiliation:
Experimental Psychology Laboratory, Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece
S. Papadopoulos
Affiliation:
Experimental Psychology Laboratory, Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece
V.-M. Papakosta
Affiliation:
Experimental Psychology Laboratory, Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece
S. Kalogerakou
Affiliation:
Experimental Psychology Laboratory, Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece
C. Poulopoulou
Affiliation:
Experimental Psychology Laboratory, Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece
E. Tsaltas
Affiliation:
Experimental Psychology Laboratory, Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece
G. Papadimitriou
Affiliation:
Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece

Abstract

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Rationale:

In the rewarded alternation model of obsessive compulsive disorder (OCD), the serotonin agonist m-chlorophenylpiperazine (mCPP) increases persistent behaviour, while chronic pretreatment with selective serotonin reuptake inhibitor (SSRI-fluoxetine) but not benzodiazepine or desipramine abolishes mCPP effects. However, we noted that acute SSRI administration also causes transient persistence increases, counteracted by mCPP pretreatment.

Objectives:

This study

  1. a. further explores the apparent cross-tolerance between fluoxetine and mCPP and

  2. b. extends the model by investigating its sensitivity to dopaminergic manipulations (D2,3 agonism - quinpirole).

Methods:

In both experiments, baseline and drug testing was carried out under daily T-maze alternation training.

Exp.1:

Matched group (n=8) pairs of rats received one of the following 20-day pretreatments (daily intraperitoneal administration):

  1. 1. saline,

  2. 2. low-dose fluoxetine (2.5mg/kg),

  3. 3. low-dose mCPP (0.5mg/kg) or

  4. 4. combined fluoxetine+mCPP.

One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10mg/kg), the other with high-dose mCPP (2.5mg/kg).

Exp.2:

One group (n=12) of rats received 20-day treatment with saline, another with quinpirole (0.5 mg/kg).

Results:
Exp.1:

Saline and low-dose mCPP- or fluoxetine-pretreated animals showed significant persistence increases under both challenges, while combined low-dose fluoxetine+mCPP pretreatment afforded full protection from either challenge.

Exp.2:

Quinpirole significantly increased directional persistence after 13 administration days.

Conclusions:

These results establish the sensitivity of the rewarded alternation OCD model to D2,3receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.

Type
P03-32
Information
European Psychiatry , Volume 24 , Issue S1: 17th EPA Congress - Lisbon, Portugal, January 2009, Abstract book , January 2009 , 24-E1031
Copyright
Copyright © European Psychiatric Association 2009
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