Interaction of serotonin- and dopaminergic systems of the brain in mechanisms of latent inhibition in rats

Abstract

The activity of serotoninergic neurons of the medial raphé nucleus was turned off by local injection of the neurotoxin, 5,7-dihydroxytryptamine. Seven days later, a conditioned passive avoidance reaction was developed following 20 preexposures to the conditional stimulus (the presentation of the experimental chamber). As compared with the sham-operated control, in which 20 preexposures to the stimulus elicited latent inhibition, i.e., attenuation of the reproduction of the conditioned passive avoidance reaction, prolonged maintenance at the formed level, and lack of susceptibility to amnesia, all of the enumerated features were disturbed in animals administered the neurotoxin. The administration of haloperidol (0.5 mg/kg) 1 h prior to training reestablished the state of latent inhibition which had been disrupted by the switching off of the mesolimbic serotonin system. It is hypothesized that the process of the suppression of attention to the nonreinforced signals during the preexposure to the stimulus is achieved by the interaction of the serotoninergic and dopaminergic systems.

Haloperidol and clozapine antagonise amphetamine-induced disruption of latent inhibition of conditioned taste aversion

“…To our knowledge, there are no published studies in the LI literature in which antipsychotic drugs and their influence on LI have been investigated in the CTA paradigm. In addition, there are only a few studies investigating antipsychotic compounds in LI procedures other than CER (Solomon et al 1981, Weiner et al 1987, Loskutova et al 1990, Russig et al 2002. Experiments 2 and 3 showed that HAL or CLZ injected before pre-exposure and conditioning blocked AMPH-induced LI disruption in a CTA paradigm.…”

Paradoxical effects of low dose MDMA on latent inhibition in the rat

“…Previously, both systemic treatments which antagonise or deplete 5-HT (Solomon et al., 1978; Cassaday et al., 1993b; Shadach et al., 2000) and regionally specific 5-HT depletion have been shown to disrupt LI (Solomon et al., 1980; Loskutova et al., 1990; Loskutova, 2001; Cassaday et al., 1993a; Nelson et al., 2012). Thus, the demonstration here that acute treatment with MDMA enhances LI is entirely consistent with a modulatory role of 5-HT in the expression of LI and suggests that increased extracellular 5-HT function potentiates LI.…”

“…This effect is abolished by treatment with the indirect catecholamine agonist amphetamine (e.g., Solomon et al., 1981; Weiner et al., 1981, 1984, 1988; Gray et al., 1992; Kumari et al., 1999; Nelson et al., 2011a). LI is similarly abolished by electrolytic lesions to the medial raphe, source of the ascending projections of the indoleamine 5-hydroxytryptamine (serotonin, 5-HT) (Solomon et al., 1980), as well as by selective 5-HT depletion using the neurotoxin 5,7-dihydroxytyptamine (5,7-DHT) (Loskutova et al., 1990; Cassaday et al., 1993a; Nelson et al., 2012), and by pharmacological treatments which reduce 5-HT release (Solomon et al., 1978) or block its actions at postsynaptic 5-HT2 receptors (Cassaday et al., 1993b; Shadach et al., 2000). Conversely, LI enhancement – demonstrated when LI in controls has been systematically weakened using a reduced number of stimulus pre-exposures – has been shown using the 5-HT reuptake blocker (selective serotonergic reuptake inhibitor, SSRI) sertraline (Loskutova, 1998).…”

The role of 5-HT1A and 5-HT1B receptors in MDMA self-administration

“…A number of studies have implicated 5-HT in latent inhibition. Electrolytic, or neurotoxic 5,7 DHT, lesions of the median raphe or NAc blocked the latent inhibition effect (Loskutova, 2001;Loskutova, Luk'yanenko, & Il'yuchenok, 1990;Solomon, Nichols, Kiernan, Kamer, & Kaplan, 1980). Rats in the pre-exposure group showed greater 5-HT metabolism in the striatum and amygdala than rats in the control group, suggesting the latent inhibition effect is associated with increased 5-HTergic activity (Molodtsova, 2003).…”