On the elevated plus-maze the anxiolytic-like effects of the 5-HT1A agonist, 8-OH-DPAT, but not the anxiogenic-like effects of the 5-HT1A partial agonist, buspirone, are blocked by the 5-HT1A antagonist, WAY 100635 |
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Authors: | N Collinson G R Dawson |
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Institution: | (1) Preclinical Pharmacology Laboratory, Addiction Research Center, National Institute on Drug Abuse, DIR, NIH, P.O. Box 5180, Baltimore, MD 21224, USA, TP |
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Abstract: | Nicotine has been shown to maintain intravenous self-administration behaviour in humans and laboratory animals. However,
factors critical in the initiation of nicotine self administration are not well defined. In particular genetic differences
and effects of pre-exposure to nicotine have not been examined. Male Sprague-Dawley or Long-Evans rats were surgically prepared
with indwelling jugular catheters and 3 days later received chronic injections of nicotine (0.4 mg/kg SC) or vehicle (saline,
1 ml/kg) for 7 days in their home cage. The next day, 2-h daily test sessions were initiated, during which rats were given
the opportunity to nose-poke for nicotine infusions (0.015, 0.03 or 0.06 mg/kg per infusion) under a one-response fixed-ratio
(FR-1) schedule of reinforcement with a 20-s time out after each infusion. One hole was defined as active while pokes in the
other hole were recorded but had no scheduled consequence. The response requirement was increased progressively to five (FR-5)
over successive sessions. Both saline- and nicotine-pretreated Sprague-Dawley rats showed a preference for the active hole,
while only the saline-pretreated Long-Evans rats acquired the self-administration as defined by significant differences between
responding in the active versus the inactive holes. The Fisher (F344) and Lewis inbred strains also failed to acquire self-administration
of nicotine under these conditions. With Sprague-Dawley and Long-Evans rats that acquired the self-administration, and showed
stable levels of maintained responding for nicotine, substituting saline for the nicotine or pretreating with mecamylamine
(2.0 mg/kg SC) extinguished the behaviour. When dose per infusion was varied, an inverted U-shaped dose-response curve was
obtained. These results support previous reports that nicotine can serve as a reinforcer in rodents and demonstrate that environmental
factors such as prior nicotine exposure or genetic factors such as rat strain can affect acquisition of nicotine self-administration.
Received: 29 March 1996 / Final version: 20 August 1996 |
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Keywords: | Nicotine Reinforcement Intravenous self-administration Strain differences Rat |
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