Research ReportInhibition of apomorphine-induced conditioned place preference in rats co-injected with buspirone: Relationship with serotonin and dopamine in the striatum

- Apomorphine and a high dose of buspirone induced CPP and motor sensitization.
- A low dose of bupirone inhibited apomorphine-induced CPP and sensitization.
- Apomorphine induced a decrease of 5-HT and 5-HIAA in caudate and accumbens.
- This was reversed by low as well as high dose buspirone.
- The high dose of buspirone decreased dopamine in caudate and accumbens.

Apomorphine is a non-narcotic derivative of morphine, which acts as a dopamine agonist to produce psychostimulant like effects. Currently, apomorphine is used in patients with advanced Parkinson׳s disease, for the treatment of persistent and disabling motor fluctuations, but a constellation of addictive syndromes such as excessive over use of medication, compulsive behaviors, and disturbances of impulse control are noticed in certain patients. Research on rodent models using conditioned place preference (CPP) paradigm also shows that the drug is rewarding. Previously we have shown that repeated administration of apomorphine produces behavioral sensitization which is prevented in rats co-injected with a low (1.0 mg/kg) but not higher (2.0 mg/kg) dose of buspirone. The present study shows that rewarding effects of apomorphine (1.0 mg/kg) in a CPP paradigm are also blocked in rats co-injected with a low (1.0 mg/kg) but not higher (2.0 mg/kg) dose of buspirone. The levels of serotonin and its metabolite are decreased in the caudate as well as nucleus accumbens of rats exhibiting CPP and the decreases do not occur in animals co-injected with low or higher dose of buspirone. The levels of dopamine and its metabolites are not affected in animals exhibiting CPP; administration as well as co-administration of higher dose of buspirone decreased dopamine metabolism in the caudate as well as nucleus accumbens. The findings suggest a critical role of serotonin in the rewarding effects of apomorphine and imply that co-use of buspirone at low doses can help to control addictive syndromes in Parkinson׳s disease patients on apomorphine therapy.