We have previously reported (1) that the antihypertensive agent, ketanserin a 5-HT2A/2C antagonist, blocked cocaine-induced accumbens dopamine (DA) and serotonin (5-HT) release simultaneously with behavior (Broderick et al., PNP:2004) and (2) that caffeine exacerbated cocaine's neurochemical and behavioral responses at even low doses (Forrester and Broderick, SFN:2004). The purpose of this paper is to ascertain the effect of ketanserin (3 mg/kg ip) on the neuromolecular interactions between caffeine and cocaine (25 and 5 mg/kg ip, respectively) because of the multifaceted mechanisms of these psychostimulants via adenosine, 5-HT and DA receptors. Neuromolecular imaging (NMI) based on in vivo electrochemistry was used with BRODERICK PROBE® laurate sensors for selective and separate detection of DA and 5-HT in accumbens; infrared photobeams (San Diego Instr.) were used to monitor ambulatory and stereotypic activities at the same time as neurotransmitter signals were detected. The results showed that ketanseri...