Sanders A McDougall1, Jordan A Taylor2, Matthew J Roe2, Constance J Greenwood2. 1. Department of Psychology, California State University, 5500 University Parkway, San Bernardino, CA, 92407, USA. smcdouga@csusb.edu. 2. Department of Psychology, California State University, 5500 University Parkway, San Bernardino, CA, 92407, USA.
Abstract
RATIONALE: Drugs that stimulate 5-HT1A/1B receptors produce both tolerance and behavioral sensitization in adult rats and mice, yet it is unknown whether the same types of plasticity are evident during earlier ontogenetic periods. OBJECTIVE: The purpose of this study was to determine whether repeated treatment with selective 5-HT1A and/or 5-HT1B agonists cause tolerance and/or sensitization in preweanling rats. METHODS: In Experiments 1 and 2, male and female preweanling rats were given a single pretreatment injection of saline, the 5-HT1A agonist (R)-( +)-8-hydroxy-DPAT (8-OH-DPAT), or the 5-HT1B agonist CP-94253 on PD 20. After 48 h, rats received a challenge injection of 8-OH-DPAT or CP-94253, respectively. In Experiment 3, rats were pretreated with saline or DPAT + CP on PD 20 and challenged with the same drug cocktail on PD 22. In Experiment 4, the tolerance- or sensitization-inducing properties of 8-OH-DPAT, CP-94253, or DPAT + CP were tested after a 4-day pretreatment regimen on PD 17-20. RESULTS: On the first pretreatment day, 8-OH-DPAT, CP-94253, and DPAT + CP increased locomotion and caused hypothermia. Repeated treatment with 8-OH-DPAT (2 or 8 mg/kg) or DPAT + CP caused locomotor sensitization in preweanling rats. In contrast, tolerance to the hypothermic effects of 8-OH-DPAT (8 mg/kg), CP-94253 (5-20 mg/kg), or DPAT + CP was evident after repeated drug treatment. CONCLUSIONS: During the preweanling period, a single injection of a selective 5-HT1A or 5-HT1B agonist is capable of producing drug-induced plasticity. A pretreatment administration of 8-OH-DPAT causes both tolerance (hypothermia) and behavioral sensitization (locomotor activity) in preweanling rats, whereas repeated CP-94253 treatment results in tolerance.
RATIONALE: Drugs that stimulate 5-HT1A/1B receptors produce both tolerance and behavioral sensitization in adult rats and mice, yet it is unknown whether the same types of plasticity are evident during earlier ontogenetic periods. OBJECTIVE: The purpose of this study was to determine whether repeated treatment with selective 5-HT1A and/or 5-HT1B agonists cause tolerance and/or sensitization in preweanling rats. METHODS: In Experiments 1 and 2, male and female preweanling rats were given a single pretreatment injection of saline, the 5-HT1A agonist (R)-( +)-8-hydroxy-DPAT (8-OH-DPAT), or the 5-HT1B agonist CP-94253 on PD 20. After 48 h, rats received a challenge injection of 8-OH-DPAT or CP-94253, respectively. In Experiment 3, rats were pretreated with saline or DPAT + CP on PD 20 and challenged with the same drug cocktail on PD 22. In Experiment 4, the tolerance- or sensitization-inducing properties of 8-OH-DPAT, CP-94253, or DPAT + CP were tested after a 4-day pretreatment regimen on PD 17-20. RESULTS: On the first pretreatment day, 8-OH-DPAT, CP-94253, and DPAT + CP increased locomotion and caused hypothermia. Repeated treatment with 8-OH-DPAT (2 or 8 mg/kg) or DPAT + CP caused locomotor sensitization in preweanling rats. In contrast, tolerance to the hypothermic effects of 8-OH-DPAT (8 mg/kg), CP-94253 (5-20 mg/kg), or DPAT + CP was evident after repeated drug treatment. CONCLUSIONS: During the preweanling period, a single injection of a selective 5-HT1A or 5-HT1B agonist is capable of producing drug-induced plasticity. A pretreatment administration of 8-OH-DPAT causes both tolerance (hypothermia) and behavioral sensitization (locomotor activity) in preweanling rats, whereas repeated CP-94253 treatment results in tolerance.
Authors: Michael D Berquist; Sebastian Leth-Petersen; Jesper Langgaard Kristensen; William E Fantegrossi Journal: Psychopharmacology (Berl) Date: 2019-11-15 Impact factor: 4.530
Authors: David Alter; Joel A Beverley; Ronak Patel; Carlos A Bolaños-Guzmán; Heinz Steiner Journal: J Psychopharmacol Date: 2017-07-18 Impact factor: 4.153