Rats were treated as described above, and sacrificed 1 or 8 d after self-administration or 1 h or 7 d after the final binge METH or saline exposure. Hippocampal serotonin (5-hydroxytryptamine; 5HT) content and transporter (SERT) function were assessed.
METH self-administration per se had no persistent effect on hippocampal 5HT content or SERT function. However, this treatment attenuated the persistent, but not acute, hippocampal serotonergic deficits caused by a subsequent repeated, high-dose, non-continent METH treatment administered 1 d the last self-administration session. No attenuation in persistent deficits were seen when the high-dose administration of METH occurred 15 d after the last self-administration session.
The present findings demonstrate that METH self-administration alters serotonergic neurons so as to engender ¡°tolerance¡± to the persistent serotonergic deficits caused by a subsequent METH exposure. However, this ¡°tolerance¡± does not persist. These data provide a foundation to investigate complex questions including how the response of serotonergic neurons to METH may contribute to contingent-related disorders such as dependence and relapse.