Kappa-opioid receptor stimulation quickens pathogenesis of compulsive checking in the quinpirole sensitization model of obsessive-compulsive disorder (OCD).

2007 ◽  
Vol 121 (5) ◽  
pp. 976-991 ◽  
Author(s):  
Melissa L. Perreault ◽  
Philip Seeman ◽  
Henry Szechtman
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Obsessive Compulsive ◽  
Kappa Opioid ◽  
Receptor Stimulation ◽  
Compulsive Disorder ◽  
Compulsive Checking

Kappa-opioid peptide receptor stimulation increases cytosolic pH and myofilament responsiveness to Ca2+ in cardiac myocytes

1991 ◽  
Vol 261 (5) ◽  
pp. H1671-H1674 ◽  
Author(s):  
C. Ventura ◽  
M. C. Capogrossi ◽  
H. A. Spurgeon ◽  
E. G. Lakatta
Keyword(s):  
Cardiac Myocytes ◽  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Methane Sulfonate ◽  
Receptor Stimulation ◽  
Cytosolic Ph ◽  
Prolonged Incubation ◽  
Ventricular Cells ◽  
Stimulation Of

Although kappa- and delta-opioid receptors on mammalian cardiac myocytes have been discovered recently, the intracellular effects that result from stimulation of these receptors remain unknown. We examine the effects of a rapid and brief exposure to a kappa-opioid receptor agonist on intracellular Ca2+, pH, and cell length in individual isolated rat ventricular cells. The specific kappa-agonist trans-dl-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzene-acetamide (U-50488H) (methane sulfonate salt) caused a transient increase in cytosolic pH (pHi) measured from the change in SNARF-1 fluorescence and an increase in cytosolic [Ca2+] (Cai), indexed by a change in indo-1 fluorescence. The initial Cai increase often was followed by Cai oscillations. Both pHi and Cai effects were blocked by the specific antagonist kappa-opioid receptor l-(N-furylmethyl)-alpha-normetazocine methane-sulfonate (Mr 1452). The amplitude of contraction that accompanied the Cai increase elicited by U-50488H was greater than that associated with a similar increase in Cai elicited by electrical stimulation or by the rapid exposure of cells to caffeine. Thus an acute and brief kappa-opioid receptor stimulation of cardiac cells leads to an increase in Cai and pHi. The pHi increase was abolished by 1) blockade of the Na(+)-H+ exchanger by ethyl isopropyl amiloride and 2) inhibition of protein kinase C (PKC) activity via pretreatment with staurosporine or prolonged incubation with 4 beta-phorbol 12-myristate 13-acetate. These maneuvers did not abolish the U-50488H-induced increase in Ca.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Enhanced reward-facilitating effects of d-amphetamine in rats in the quinpirole model of obsessive–compulsive disorder

2013 ◽  
Vol 16 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
Timo T. Schmidt ◽  
Ellis Rea ◽  
Julia Shababi-Klein ◽  
George Panagis ◽  
Christine Winter
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Reward Processing ◽  
Brain Stimulation Reward ◽  
Repetitive Behaviours ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Before And After ◽  
Compulsive Checking ◽  
Compulsive Behaviour ◽  
Monopolar Stimulation

Abstract The underlying neurobiology of addictive or repetitive behaviours, such as obsessive–compulsive disorder (OCD), involves dopaminergic dysregulation. While addictive behaviour depends strongly on mesolimbocortical dopaminergic responses, repetitive behaviours have been associated with dopaminergic dysregulation in the basal ganglia–thalamo–cortical circuitry. The present study investigates differences in brain stimulation reward in rats with quinpirole-induced compulsive checking behaviour, in order to examine if deficits in reward processing are also relevant for OCD. Rats were tested in the intracranial self-stimulation (ICSS) paradigm, which targets reward-related responses. After phenotype induction, animals were implanted with a monopolar stimulation electrode in the left medial forebrain bundle and trained to press a lever to self-administer electric stimulation of varying frequency. The curve-shift method was used to assess the reward-facilitating effects of d-amphetamine and the reward-attenuating effects of haloperidol (a D2 antagonist). Thresholds for ICSS were estimated before and after drug/saline injection. The reward-facilitating effects of d-amphetamine were enhanced in quinpirole-treated rats in comparison to controls. This finding suggests that chronic quinpirole-treatment induces changes within the reward circuitry relevant for compulsive behaviour in the rat.

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