The discriminative stimulus properties of cocaine: Effects of microinfusion of cocaine, a 5-HT(1A) agonist or antagonist, into the ventral tegmental area

Serotonin (5-HT) afferents may modulate the dopamine mesoaccumbens circuit, which has been shown to be critically involved in the locomotor stimulatory, discriminative stimulus, and rewarding properties of cocaine. In the present study, we investigated the role of 5-HT(1A) receptors in the ventral tegmental area (VTA) in mediating the discriminative stimulus effects of cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task. After acquiring the cocaine-saline discrimination, rats were stereotaxically implanted with bilateral guide cannulae into the VTA or adjacent substantia nigra reticulata (SNR). Intraperitoneal administration of cocaine (0.625-10 mg/kg) produced a dose-related increase in drug-lever responding. Both intra-VTA and intra-SNR infusion of cocaine (12.5-50 μg/0.5 μl/side) engendered primarily saline-like responding. Microinjection of the 5-HT(1A) agonist 8-hydroxy-2-(di-N-propylamino) tetralin (DPAT; 0.1-10 μg/0.5 μl/side) or the 5-HT(1A) antagonist WAY 100635 (0.01-1.0 μg/0.5 μl/side) into the VTA or SNR did not substitute for the systemic cocaine cue. Further, intra-VTA or intra-SNR DPAT or WAY 100635 in combination with systemic doses of cocaine did not alter (i.e., attenuate or potentiate) the systemic cocaine cue. Overall, these data indicate that 5-HT(1A) receptors in the VTA do not mediate or modulate the discriminative stimulus effects of cocaine in the rat.