Effect of dopamine and serotonin receptor antagonists on fencamfamine-induced abolition of latent inhibition

Abstract

The purpose of this investigation was to verify the role of dopamine and serotonin receptors in the effect of fencamfamine (FCF) on latent inhibition. FCF is a psychomotor stimulant with an indirect dopaminergic action. Latent inhibition is a model of attention. Latent inhibition is blocked by dopaminergic agents and facilitated by dopamine receptor agonists. FCF has been shown to abolish latent inhibition. The serotonergic system may also participate in the neurochemical mediation of latent inhibition. The selective dopamine D(1) receptor antagonist SCH 23390 (7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol), D(2) receptor antagonists pimozide (PIM) and methoclopramide (METH), and serotonin 5-HT(2A/C) receptor antagonist ritanserin (RIT) were used in the present study. Latent inhibition was evaluated using a conditioned emotional response procedure. Male Wistar rats that were water-restricted were subjected to a three-phase procedure: preexposure to a tone, tone-shock conditioning, and a test of the effect of the tone on licking frequency. All of the drugs were administered before the preexposure and conditioning phases. The results showed that FCF abolished latent inhibition, and this effect was clearly antagonized by PIM and METH and moderately attenuated by SCH 23390. At the doses used in the present study, RIT pretreatment did not affect latent inhibition and did not eliminate the effect of FCF, suggesting that the FCF-induced abolition of latent inhibition is not mediated by serotonin 5-HT(2A/C) receptors. These results suggest that the effect of FCF on latent inhibition is predominantly related to dopamine D(2) receptors and that dopamine D(2) receptors participate in attention processes.

New Drugs on the Internet: The Case of Camfetamine

“…It was also shown that FCF can act as a positive reinforcer and was hypothesized that opioid receptors mediate the reinforcing effects of FCF [25]. Furthermore, changes in the sensitivity of pre- or postsynaptic DA receptors might underlie both tolerance and sensitization to the effects induced by long-term FCF administration [26, 27]. Some authors suggest that chronic FCF treatment is linked to a modification in Na,K-ATPase activity through the cyclic AMP-dependent protein kinase, nitric oxide synthase (NOS) activity, and cyclic GMP levels in the nucleus accumbens (NAc) and striatum (ST) [28].…”

ASD and ADHD as syndromes of high creativity - Le TSA et le TDAH comme syndromes de haute créativité

“…Alterations in concentration levels and neurotransmission receptors related to γaminobutyric acid, acetylcholine, dopamine, glutamic acid, serotonin have been reported in ADHD and ASD (table 1) and genetic variations related to these same neurotransmitters have also been reported in ADHD and ASD (table 2). Carson (2011) noticed that genetic research relating to dopamine and serotonin are associated with the search for novelty and reduced latent inhibition (de Aguiar et al, 2013;Swerdlow et al, 2003) or even cognitive flexibility and working memory. However, in addition to dopamine and serotonin, other neurotransmitters may be involved in creativity and neurodevelopmental disorders.…”

“…Carson (2011) a remarqué que les recherches génétiques relatives à la dopamine et à la sérotonine sont associées à la recherche de la nouveauté et à une inhibition latente réduite (de Aguiar et al, 2013 ;Swerdlow et al, 2003) ou encore à la flexibilité cognitive et à la mémoire de travail. Cependant, outre la dopamine et la sérotonine, d'autres neurotransmetteurs pourraient être impliqués dans la créativité et les troubles neurodéveloppementaux.…”