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.