Effects of fendiline on cocaine-seeking behavior in the rat.
BACKGROUND
L-type Ca(2+) channels (LTCC) and GABAB receptors are both possible targets in the development of new pharmacological compounds for cocaine addiction. Drugs that target either receptor attenuate a wide range of cocaine-seeking behaviors in the rat. However, there is no current human-approved pharmacotherapeutic intervention for psychostimulant addiction.


OBJECTIVE
This study examined the effects of a human-approved LTCC blocker, fendiline, on cocaine-taking and cocaine-seeking behavior in rats. The effects of combining fendiline with the GABAB receptor agonist baclofen on cocaine self-administration were also tested.


METHODS
Male Wistar rats were trained to self-administer cocaine, and the effects of fendiline pretreatment (vehicle, 1.78, 3.16, 5.62 mg/kg, intraperitoneal (IP)) were tested on progressive ratio responding and cue- and drug-induced reinstatement. The effects of baclofen (vehicle, 0.56, 1.78, 3.16, 5.62 mg/kg, IP) combined with fendiline (5.62 mg/kg, IP) were tested on progressive ratio responding. Control experiments measured locomotor activity and lever pressing for food in rats that received both baclofen and fendiline prior to the test session.


RESULTS
Acute injections of fendiline prior to cue- or drug-induced reinstatement significantly attenuated lever-pressing behavior (p < 0.05). Fendiline and baclofen, but not fendiline alone, not only significantly attenuated breakpoints, but also impaired general motor behavior and naturalistic reinforcement (p < 0.05).


CONCLUSIONS
These data suggest that the LTCC blocker fendiline may represent a novel pharmacotherapeutic intervention to prevent reinstatement to cocaine seeking. Also, co-administration of fendiline and baclofen not only can attenuate the motivation to take cocaine, but also impairs general motor behavior and naturalistic reinforcement.
Department of Psychiatry, University of British Columbia, Detwiller Pavilion, 2255 Wesbrook Mall, Vancouver, British Columbia, V6T 2A1, Canada. Jcunningham@alumni.ubc.ca.
Jonathan J
JJ
Cunningham
Department of Psychology, St. Francis Xavier University, 2320 Notre Dame Blvd., Antigonish, Nova Scotia, B2G 2W5, Canada.
Erin
E
Orr
Department of Psychology, St. Francis Xavier University, 2320 Notre Dame Blvd., Antigonish, Nova Scotia, B2G 2W5, Canada.
Barbara C
BC
Lothian
Department of Psychology, St. Francis Xavier University, 2320 Notre Dame Blvd., Antigonish, Nova Scotia, B2G 2W5, Canada.
Jennifer
J
Morgen
Department of Psychology, St. Francis Xavier University, 2320 Notre Dame Blvd., Antigonish, Nova Scotia, B2G 2W5, Canada. kbrebner@stfx.ca.
Karen
K
Brebner
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D016739:Behavior, Addictive / Q000188:drug therapy; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D005275:Fendiline / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration
D002121:Calcium Channel Blockers; D000697:Central Nervous System Stimulants; D001418:Baclofen; D003042:Cocaine; D005275:Fendiline
Addiction; Cocaine; Fendiline; GABAB receptor; L-type calcium channel antagonist; Reinstatement; Self-administration