Intracranial Drug Self-administration

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I summarize astudy that produced significant results during the fisical year 2010. The ability to invigorate responding for salient stimuli has been known as a hallmark of ventral striatal dopamine. For example, injections of amphetamine into the ventral striatum facilitate conditioned reinforcement, in which sensory stimuli previously paired with primary reinforcers like food will powerfully instigate responding. More recently, we show that amphetamine administered into the ventral striatum facilitate responding for unconditioned visual signals in rats. Here we show that noncontingent administration of baclofen into the median (MR) or dorsal (DR) raphe nuclei facilitates rats responding for salient visual signals. Rats received baclofen infusions into either the MR or DR on a fixed-interval schedule. Effects of 3 different concentrations of baclofen were examined on lever-pressing. An active lever response illuminated a cue light just above the lever for one sec, while an inactive lever response had no programmed consequence. In the absence of baclofen administration, rats responded on the active lever more than the inactive lever. Non-contingent administration of baclofen into the MR or DR increased responses on both the active and inactive levers. The MR mediated increased lever-pressing at a lower concentration of baclofen than the DR did. In the absence of visual signal reinforcement, intra-MR baclofen did not significantly increase lever-pressing or locomotor activity, whereas in the presence of visual signal reinforcement, baclofen increased both. Heightened locomotor activity induced by intraperitoneal injections of amphetamine failed to concur with increased lever-pressing for visual signals. These results indicate that the observed enhancement of visual signal seeking is distinct from an enhancement of general locomotor activity. Seeking for visual signal decreased when baclofen was co-administered with the GABAB receptor antagonist, SCH 50911, confirming the involvement of local GABAB receptors. Seeking for visual signal also abated when baclofen administration was preceded by intraperitoneal injections of the dopamine antagonist, SCH 23390 (0.025mg/kg), suggesting enhanced visual signal seeking depends on intact dopamine signals. Because GABAB receptors are selectively expressed on serotonergic neurons in the MR, the enhancement of visual signal seeking may be mediated by tonic inhibition of serotonergic neurons. In any case, our data suggest that baclofen administration into the midbrain raphe, particularly MR, facilitates responding for salient stimuli, an effect that is known as a hallmark of ventral striatal dopamine.