Source Paper
Enhancement of Locomotor Activity and Conditioned Reward to Cocaine by Brain-Derived Neurotrophic Factor
Brian A. Horger, Christiana A. Iyasere, Melissa T. Berhow, Chad J. Messer, Eric J. Nestler et al.
Journal of Neuroscience • 1999
Conditioned Reward Response with BDNF
Objective: To investigate the effects of brain-derived neurotrophic factor (BDNF) infusions into the nucleus accumbens on cocaine-induced locomotor sensitization and responding for conditioned reinforcers, with and without cocaine administration
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Equipment3
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Protocol Steps
Surgical implantation of minipumps
Chronically implanted minipumps were surgically placed to deliver BDNF into the nucleus accumbens or ventral tegmental area
Note: BDNF dose: 1-2.5 μg/d
View evidence from paper
“BDNF was infused into the nucleus accumbens (NAc) or ventral tegmental area over 2 weeks via chronically implanted minipumps (1–2.5 μg/d)”
Experiment 1: Cocaine administration and locomotor activity measurement
Cocaine was administered via intraperitoneal injection at doses of 5-15 mg/kg to BDNF-treated and control animals, and psychomotor stimulant effects were measured
Note: BDNF enhanced initial stimulant effects and facilitated development of sensitization to repeated cocaine doses
View evidence from paper
“the psychomotor stimulant effects of cocaine (5–15 mg/kg, i.p.) were studied. We found that BDNF enhanced the initial stimulant effects of cocaine and seemed to facilitate the development of sensitization”
Experiment 2: Conditioned reinforcer responding with saline
Saline was first administered and responding on the conditioned reinforcer lever was measured in BDNF-treated and control rats
Note: BDNF-treated rats showed twice as many CR responses compared with controls
View evidence from paper
“BDNF-treated rats showed twice as many CR responses compared with controls when saline was first administered”
Experiment 2: Conditioned reinforcer responding with cocaine
Cocaine (10 mg/kg, i.p.) was administered and responding on the conditioned reinforcer lever was measured in BDNF-treated and control rats
Note: BDNF enhanced responding on CR lever more than four times that seen in control animals
View evidence from paper
“BDNF enhanced responding on the CR lever more than four times that seen in control animals after a cocaine injection (10 mg/kg, i.p.)”
Long-term follow-up measurement
Conditioned reinforcer responding was measured for more than a month after BDNF infusions had stopped
Note: Enhanced response to cocaine in BDNF-treated animals persisted, indicating long-lasting changes
View evidence from paper
“The enhanced response to cocaine in BDNF-treated animals persisted for more than a month after the BDNF infusions had stopped”
Experiment 3: Locomotor sensitization in BDNF knock-out mice
Locomotor sensitization to cocaine was examined in heterozygous BDNF knock-out mice and compared with wild-type littermates
Note: Development of sensitization was delayed in BDNF knock-out mice compared with wild-type littermates
View evidence from paper
“In experiment 3, we examined locomotor sensitization to cocaine in heterozygous BDNF knock-out mice and found that the development of sensitization was delayed compared with wild-type littermates”