Extending therapeutic use of psychostimulants: focus on serotonin-1A receptor.

BACKGROUND

Despite a number of medicinally important pharmacological effects, the therapeutic use of psychostimulants is limited because of abuse potential and psychosis following long term use. Development of pharmacological agents for improving and extending therapeutic use of psychostimulants in narcolepsy, attention deficit hyperactivity disorder, Parkinson's disease, obesity and as cognitive enhancer is an important research imperative. In this regard, one potential target system is the 5-hydroxytryptamine (5-HT; serotonin) neurotransmitter system. The focus of the present article is to evaluate a potential role of 5-HT-1A receptor in the alleviation of abuse potential and psychosis-induced by prescription psychostimulants amphetamines and apomorphine.

METHODS

Synaptic contacts between dopamine systems and 5-HT-1A receptors are traced. Studies on serotonin-1A influences on the modulation of dopamine neurotransmission and psychostimulant-induced behavioral sensitization are accumulated.

RESULTS

Inhibition of amphetamine and apomorphine-induced behavioral sensitization by co administration of 5-HT-1A agonists cannot be explained in terms of direct activation of 5-HT-1A receptors, because activation of pre- as well as postsynaptic 5-HT-1A receptors tends to increase dopamine neurotransmission.

CONCLUSIONS

Long term use of amphetamine and apomorphine produces adaptive changes in 5-HT-1A receptor mediated functions, which are prevented by the co-use of 5-HT-1A agonists. In view of extending medicinal use of psychostimulants, it is important to evaluate the effects of co-use of 5-HT-1A agonists on potential therapeutic profile of amphetamine and apomorphine in preclinical research. It is also important to evaluate the functional significance of 5-HT-1A receptors on psychostimulant-induced behaviors in other addiction models such as drug self-administration and reinstatement of drug seeking behavior.