Dopamine and serotonin metabolism associated with morphine reward and its inhibition with buspirone: A study in the rat striatum

Adaptations within the nucleus accumbens (NAc) and caudate nucleus (CN) dopamine neurotransmission are involved in behavioral sensitization and enhanced incentive motivation towards drug paired stimuli which lead to drug addiction. Serotonin (5-hydroxytryptamine; 5-HT) can modulate dopamine neurotransmission to reduce rewarding effects of drugs of abuse. A recent study from our laboratory shows that rewarding effects of morphine are inhibited in rats co-treated with buspirone. To understand the neurochemical mechanism involved in morphine addiction and its inhibition with buspirone, present study determines the effects of buspirone, morphine and their co-administration on the metabolism of serotonin and dopamine in the NAc and CN. We find that rewarding effects of morphine are associated with an enhancement and attenuation of dopamine metabolism, respectively in the CN and NAc. Serotonin metabolism is enhanced in both regions. Co-administration of buspirone not only prevents rewarding effects of morphine, but its effects on the metabolism of dopamine and serotonin in the NAc and CN are also reversed. Results suggest that 5-HT1A receptor dependent modulation of dopamine neurotransmission in the CN and NAc is involved in the modulation of the rewarding effects of morphine in buspirone co-treated animals. The findings documenting an important role of 5-HT1A receptors in drug addiction suggest that synthetic opioid drugs with agonist activity of 5-HT1A receptors may prove non addictive analgesics.