| Autor: |
Hillhouse, Todd M., Porter, Joseph H., Negus, S. Stevens |
| Předmět: |
|
| Zdroj: |
Drug Development Research; Dec2014, Vol. 75 Issue 8, p479-488, 10p |
| Abstrakt: |
Preclinical Research N ‐ methyl ‐ D ‐ aspartate (NMDA) receptor antagonists, such as ketamine, have emerged as novel candidate treatments for major depressive disorder, but abuse potential of these agents is a concern. The NMDA antagonist phencyclidine has known abuse liability but undefined efficacy as an antidepressant. To further evaluate the relationship between antidepressant ‐ like and abuse ‐ related effects of NMDA antagonists, this study evaluated the effects of phencyclidine (1.0 – 10.0 mg/kg) in male Sprague ‐ Dawley rats responding under two procedures that have been used to assess antidepressant ‐ like effects (differential ‐ reinforcement ‐ of ‐ low ‐ rate [DRL] 72 s schedule of food reinforcement; n = 9) and abuse ‐ related drug effects (intracranial self ‐ stimulation [ICSS]; n = 6). Under the DRL 72 s schedule, phencyclidine (10.0 mg/kg) increased reinforcers and decreased responses without shifting the peak location of the interresponse time (IRT) distribution. Ketamine (10.0 mg/kg) also increased reinforcers and decreased responses, but unlike phencyclidine, it produced a rightward shift in the peak location of the IRT distribution. The 10.0 mg/kg phencyclidine dose that decreased DRL 72 s responding also decreased rates of ICSS for 50 min after its administration; however, abuse ‐ related ICSS facilitation was observed at later times (100 – 300 min) or after a lower phencyclidine dose (3.2 mg/kg). These results suggest that phencyclidine produces weaker antidepressant ‐ like effects, but stronger abuse ‐ related effects than ketamine in these procedures. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text