Dual dopamine/serotonin treatment approach for addictive behaviour
Degree GrantorUniversity of Canterbury
Degree NameMaster of Science
Illicit drug abuse and addiction is a major problem in New Zealand and worldwide with approximately 12% of illicit drug users classified as having drug dependence or drug-use disorders. The chronically relapsing nature of drug addiction is a prominent feature of this disorder and a significant barrier to treating addiction. Amphetamine-type drugs, more than any other class of drugs, have seen an increase in global usage since the early 1990's. The lack of approved medications for the treatment of stimulant addiction together with an increasing treatment demand drives the need for pharmaceutical intervention. Substitute treatment approaches primarily focus on the dopamine (DA) system. However, several lines of research implicate a dual role for serotonin (5-HT). Using a benztropine (BZT) analogue, JHW 007 (JHW), and an atypical antidepressant, trazodone (TRAZ), we sought to test whether the combined modulation of DA and 5-HT during a period of extinction produced greater attenuation to drug-induced reinstatement compared to either DA or 5-HT alone. One hundred and two (102) male Long Evans rats were tested using an extinction-reinstatement model of methamphetamine (MA) addiction in conditioned place preference (CPP) (n=72) and self-administration (n=30) experimental designs. We hypothesised that a combined DA/5-HT treatment would further attenuate MA-induced reinstatement. Findings showed that JHW significantly attenuated MA-induced reinstatement in our self-administration model but not CPP, while TRAZ failed to significantly attenuate reinstatement in both experiments. The combination treatment group showed a mild attenuation to drug seeking with CPP, but this finding was not significant. Due to time restrictions, we did not test the combination group using a self-administration procedure. Unfortunately we were unable to fully address our initially proposed hypothesis, but our results with JHW add further support to this BZT analogue as a promising stimulant abuse medication.