Abstract
Manipulation of the serotonin (5-HT)1B receptors can modify the behavioral effects of amphetamine including its reinforcing properties. Focus of this study was to examine changes in 5-HT1B receptor protein expression in several brain structures linked to substance drug disorder in different stages of amphetamine addiction—single session of amphetamine self-administration, 20 consecutive days of amphetamine self-administration, and 3 and 14 days of extinction from chronic drug intake. “Yoked” procedure was employed to set apart pharmacological and motivational effects of amphetamine intoxication. Immunohistofluorescence was performed on brain slices containing the following regions: nucleus accumbens (NAc) shell and core, globus pallidum (GP) lateral and ventral, hippocampus (HIP), substantia nigra (SN), and ventral tegmental area (VTA). Single amphetamine session decreased the amount of 5-HT1B receptors in SN, VTA, and HIP in active and yoked rats. On the contrary, 20 days of chronic amphetamine exposure triggered elevation of 5-HT1B receptors exclusively in animals that voluntarily administered the drug in NAc core, GP ventral, and HIP. Furthermore, 14-day (but not 3-day) extinction from amphetamine increased the 5-HT1B receptor expression in ventral and lateral GP, HIP, and SN. This study is the first to demonstrate that exposure to amphetamine and its extinction alter the expression of 5-HT1B receptors in various rat brain regions, and those changes seem to be transient and region specific. Importantly, since increased expression of 5-HT1B receptor after chronic amphetamine self-administration was limited only to active group of animals, we suggest that 5-HT1B receptor is linked to motivational aspect of addiction.
Highlights
Serotonin (5-HT) transmission originates in raphe nuclei and spreads throughout the brain innervating almost all its parts (Parent et al 1981; Steinbusch 1981)
Animals that were introduced to single 2-h amphetamine session scored 38.4 ± 9.4 lever presses on the active lever and 6.7 ± 3.1 on the inactive, receiving on average 1.6 ± 0.1 mg/kg amphetamine per rat
The two-way analysis of variance (ANOVA) for repeated measures showed that from the day 11 to the end of the maintenance phase, the number of active lever presses was statistically greater than the number of the inactive lever presses (p < 0.05; Fig. 1a–c)
Summary
Serotonin (5-HT) transmission originates in raphe nuclei and spreads throughout the brain innervating almost all its parts (Parent et al 1981; Steinbusch 1981). HT1B receptor exhibited increased sensitivity to amphetamine measured as increased in locomotor activity (Bronsert et al 2001) When these receptors were pharmacologically stimulated, they enhanced amphetamineinduced hyperlocomotion (Papla et al 2002) and facilitated the development of sensitization (Przegalinski et al 2001) and decreased the number of lever presses in fixed and progressive ratio schedule (Fletcher et al 2002; Miszkiel et al 2012) in amphetamine self-administration model. In the latter animal paradigm, administration of 5-HT1B receptors antagonist attenuated the amphetamine-evoke seeking behavior (Miszkiel et al 2012). This study was designed to determine the potential alternations in 5-HT1B receptor protein level across different aspects of amphetamine addiction in rats
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