We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in rats.
Psychopharmacology 2000 July
RATIONALE: Human positron emission tomography (PET) shows that striatal dopamine D2 receptor occupancy predicts extrapyramidal side effects (EPS). Patients showed a clinical response with > or = 65% D2 occupancy, but EPS only when D2 occupancy >78%. Catalepsy and the selective suppression of conditioned avoidance response (CAR) are often used as animal models to predict EPS and antipsychotic effect, respectively. However, the quantitative relationship between striatal D2 occupancy and effects in these models is not known.
OBJECTIVES: The present study intended to investigate the relationship between animal catalepsy, suppression of CAR, and D2 receptor blockade using a method of evaluating D2 receptor occupancy similar in principle to that used in patients.
METHODS: In vivo binding of [11C]-raclopride and [3H]-raclopride was compared. Doses of cold raclopride were chosen to provide a D2 occupancy from 0 to 95%. The relationship between dose/time course of catalepsy and D2 occupancy was assessed. Effects of raclopride on conditioned avoidance response (CAR) behavior were tested.
RESULTS: In vivo binding of [11C]-raclopride compared to [3H]-raclopride was virtually the same. Using [3H]-raclopride, cold raclopride (0.01-0.2 mg/kg) produced 16-77% D2 receptor occupancy and no catalepsy. Raclopride (0.5-2 mg/kg) produced 83-95% D2 occupancy and significant catalepsy. Raclopride (2 mg/kg) produced on average 95% and 87% D2 receptor occupancy 1 and 2 h after administration, respectively, and maximum catalepsy. D2 occupancy at 4, 8 and 24 h was on average 58%, 46%, and 4%, respectively. No catalepsy was observed. Raclopride (0.2 mg/kg), estimated at 70-75% D2 occupancy, produced suppression of CAR.
CONCLUSIONS: In vivo D2 occupancy measurements in rats using [3H]-raclopride is analogous to using [11C]-raclopride in human PET scanning. Suppression of CAR occurred at a D2 occupancy of around 70-75%, and catalepsy at D2 occupancy >80%. Results closely resembled human studies where 65-70% D2 occupancy was required for antipsychotic response, while > or = 80% D2 occupancy led to EPS. Brain mechanisms involved in mediation of catalepsy in rats and EPS in humans might indeed be similar. Both suppression of CAR in rats and antipsychotic response in humans might share an underlying construct, i.e. the need for around 70% D2 receptor blockade.
OBJECTIVES: The present study intended to investigate the relationship between animal catalepsy, suppression of CAR, and D2 receptor blockade using a method of evaluating D2 receptor occupancy similar in principle to that used in patients.
METHODS: In vivo binding of [11C]-raclopride and [3H]-raclopride was compared. Doses of cold raclopride were chosen to provide a D2 occupancy from 0 to 95%. The relationship between dose/time course of catalepsy and D2 occupancy was assessed. Effects of raclopride on conditioned avoidance response (CAR) behavior were tested.
RESULTS: In vivo binding of [11C]-raclopride compared to [3H]-raclopride was virtually the same. Using [3H]-raclopride, cold raclopride (0.01-0.2 mg/kg) produced 16-77% D2 receptor occupancy and no catalepsy. Raclopride (0.5-2 mg/kg) produced 83-95% D2 occupancy and significant catalepsy. Raclopride (2 mg/kg) produced on average 95% and 87% D2 receptor occupancy 1 and 2 h after administration, respectively, and maximum catalepsy. D2 occupancy at 4, 8 and 24 h was on average 58%, 46%, and 4%, respectively. No catalepsy was observed. Raclopride (0.2 mg/kg), estimated at 70-75% D2 occupancy, produced suppression of CAR.
CONCLUSIONS: In vivo D2 occupancy measurements in rats using [3H]-raclopride is analogous to using [11C]-raclopride in human PET scanning. Suppression of CAR occurred at a D2 occupancy of around 70-75%, and catalepsy at D2 occupancy >80%. Results closely resembled human studies where 65-70% D2 occupancy was required for antipsychotic response, while > or = 80% D2 occupancy led to EPS. Brain mechanisms involved in mediation of catalepsy in rats and EPS in humans might indeed be similar. Both suppression of CAR in rats and antipsychotic response in humans might share an underlying construct, i.e. the need for around 70% D2 receptor blockade.
Full text links
Related Resources
Trending Papers
Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.Endocrine Reviews 2024 April 28
The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.Circulation 2024 April 26
Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials.European Journal of Medical Research 2024 April 19
Interstitial Lung Disease: A Review.JAMA 2024 April 23
Ventilator Waveforms May Give Clues to Expiratory Muscle Activity.American Journal of Respiratory and Critical Care Medicine 2024 April 25
Acute Kidney Injury and Electrolyte Imbalances Caused by Dapagliflozin Short-Term Use.Pharmaceuticals 2024 March 27
Systemic lupus erythematosus.Lancet 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app