Effects of Fendiline on Cocaine-seeking Behavior in the Rat

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2015 Sep 9

PMID 26345344

Citations 3

Authors

Jonathan J Cunningham

Erin Orr

Barbara C Lothian

Jennifer Morgen

Karen Brebner

Affiliations

Soon will be listed here.

Abstract

Rationale: 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.

Objectives: 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).

Conclusion: 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.

Citing Articles

Ca1.3 L-type Ca channel-activated CaMKII/ERK2 pathway in the ventral tegmental area is required for cocaine conditioned place preference.

Martinez-Rivera A, Hao J, Rice R, Inturrisi C, Rajadhyaksha A Neuropharmacology. 2022; 224:109368.

PMID: 36481277 PMC: 9796157. DOI: 10.1016/j.neuropharm.2022.109368.

The L-type calcium channel blocker, isradipine, attenuates cue-induced cocaine-seeking by enhancing dopaminergic activity in the ventral tegmental area to nucleus accumbens pathway.

Addy N, Nunes E, Hughley S, Small K, Baracz S, Haight J Neuropsychopharmacology. 2018; 43(12):2361-2372.

PMID: 29773910 PMC: 6180103. DOI: 10.1038/s41386-018-0080-2.

Differential stimulus control of drug-seeking: multimodal reinstatement.

Batten S, Beckmann J Addict Biol. 2017; 23(5):989-999.

PMID: 28791757 PMC: 5807245. DOI: 10.1111/adb.12544.

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