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Effect of the use‐dependent nicotinic receptor antagonist BTMPS on cocaine withdrawal
Author(s) -
Buccafusco Jerry J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a778-d
Subject(s) - saline , antagonist , anesthesia , behavioural despair test , medicine , discontinuation , pharmacology , receptor , hippocampus , antidepressant
We have provided evidence in support of the role of central cholinergic neurons in aspects drug abuse. This study was designed to determine whether a use‐dependent nicotinic antagonist bis (2,2,6,6‐tetramethyl‐4‐piperidinyl) sebacate (BTMPS) could block a characteristic withdrawal response to cocaine. Wistar rats (300–325 g) were divided into 3 groups. Over 5 days one (control) group received a daily regimen that consisted of an i.p. injection of saline followed 10 min later by a second saline injection. The other two groups received the following cocaine regimen: 10 mg/kg, i.p. on Days 1, 2 and 3 and 20 mg/kg on Days 4 and 5. Each cocaine injection was preceded 10 min earlier by either a saline injection, or by 0.5 mg/kg BTMPS. Rats were allowed to undergo withdrawal for 48 hours after the last injection. At that time each subject was evaluated in the forced swim test. This consisted of a cylindrical tank filled to 30 cm with room water. Each rat was placed in the water for 15 min of forced swimming during a pre‐test session. 72 hr after cocaine discontinuation, rats were evaluated for 5 min of forced swimming. The onset to immobility (floating) and the time spent in escape behavior (swimming or attempting to climb the wall) was measured. Cocaine withdrawal was associated with a significant decrease in the onset to immobility relative to the saline‐saline and the BTMPS‐cocaine groups. Cocaine withdrawal also was associated with a significant decrease in the duration of escape behavior relative to the saline‐saline (P<0.047) and the BTMPS‐cocaine groups. Thus BTMPS treatment during cocaine administration inhibited the expression of subsequent withdrawal behavior.