RATIONALE: Alterations in serotonin (5-HT) neurotransmission during cocaine withdrawal may be involved in incentive motivation for cocaine. OBJECTIVE: The present study examined the effects of 5-HT depletion on cocaine- and food-seeking behavior (i.e., non-reinforced operant responding). METHODS: Separate groups of rats were trained to lever press for cocaine infusions (0.33 mg/kg/0.1 ml, i.v.) or for food pellets (45-mg Noyes food pellets) on a fixed-ratio one schedule of reinforcement during 14 daily 2-h sessions. Half of each group then received treatment with either saline or the tryptophan hydroxylase inhibitor para-chlorophenylalanine (p-CPA; 100 mg/kg, i.p.) on post-training day 5 and day 6. Twenty-four hours after their last treatment, rats were tested for cocaine- or food-seeking behavior by measuring operant responding in the absence of reinforcement until they reached an extinction criterion of no responses for 30 min. Animals were sacrificed 24 h after testing and brain 5-HT levels in various regions were quantified. RESULTS: In cocaine-trained animals, p-CPA treatment significantly decreased cocaine-seeking behavior and produced a trend toward a decrease in extinction latency relative to saline treatment. In food-trained animals, p-CPA treatment failed to alter any of the behavioral measures during testing, suggesting that p-CPA treatment did not alter the animals' memory or ability to perform an operant response. p-CPA significantly depleted 5-HT by 73-85% in every brain region examined. CONCLUSION: The results suggest that decreasing 5-HT neurotransmission may decrease incentive motivation for cocaine.
RATIONALE: Alterations in serotonin (5-HT) neurotransmission during cocaine withdrawal may be involved in incentive motivation for cocaine. OBJECTIVE: The present study examined the effects of 5-HT depletion on cocaine- and food-seeking behavior (i.e., non-reinforced operant responding). METHODS: Separate groups of rats were trained to lever press for cocaine infusions (0.33 mg/kg/0.1 ml, i.v.) or for food pellets (45-mg Noyes food pellets) on a fixed-ratio one schedule of reinforcement during 14 daily 2-h sessions. Half of each group then received treatment with either saline or the tryptophan hydroxylase inhibitor para-chlorophenylalanine (p-CPA; 100 mg/kg, i.p.) on post-training day 5 and day 6. Twenty-four hours after their last treatment, rats were tested for cocaine- or food-seeking behavior by measuring operant responding in the absence of reinforcement until they reached an extinction criterion of no responses for 30 min. Animals were sacrificed 24 h after testing and brain 5-HT levels in various regions were quantified. RESULTS: In cocaine-trained animals, p-CPA treatment significantly decreased cocaine-seeking behavior and produced a trend toward a decrease in extinction latency relative to saline treatment. In food-trained animals, p-CPA treatment failed to alter any of the behavioral measures during testing, suggesting that p-CPA treatment did not alter the animals' memory or ability to perform an operant response. p-CPA significantly depleted 5-HT by 73-85% in every brain region examined. CONCLUSION: The results suggest that decreasing 5-HT neurotransmission may decrease incentive motivation for cocaine.
Authors: Nathan S Pentkowski; Felicia D Duke; Suzanne M Weber; Lara A Pockros; Andrew P Teer; Elizabeth C Hamilton; Kenneth J Thiel; Janet L Neisewander Journal: Neuropsychopharmacology Date: 2010-06-02 Impact factor: 7.853
Authors: I Sora; F S Hall; A M Andrews; M Itokawa; X F Li; H B Wei; C Wichems; K P Lesch; D L Murphy; G R Uhl Journal: Proc Natl Acad Sci U S A Date: 2001-04-24 Impact factor: 11.205
Authors: Nathan S Pentkowski; Jazmin I Acosta; Jenny R Browning; Elizabeth C Hamilton; Janet L Neisewander Journal: Addict Biol Date: 2009-07-24 Impact factor: 4.280