Expression of brain‐derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs

Abstract

Typical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down-regulated BDNF mRNA expression in both CA1 (P < 0.05) and dentate gyrus (P < 0.01) regions compared with vehicle control. In contrast, the atypical antipsychotic agents clozapine (10 mg/kg) and olanzapine (2.7 mg/kg) up-regulated BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P < 0.01). These findings demonstrate that the typical and atypical antipsychotic drugs differentially regulate BDNF mRNA expression in rat hippocampus.

Olanzapine Attenuates the Okadaic Acid-Induced Spatial Memory Impairment and Hippocampal Cell Death in Rats

“…In addition, olanzapine can regulate the translocation and expression of pro-and antiapoptotic proteins Bax and Bcl-X L in PC12 cells (Wei et al, 2003b). In animal studies, chronic administration of olanzapine was shown to upregulate the expression of Bcl-2 and BDNF in the hippocampus (Bai et al, 2003(Bai et al, , 2004 and to help restore the repeated restrain stress-induced decrease in these two neuroprotective proteins in hippocampal neurons (Luo et al, 2004). Furthermore, the prevention of Bcl-2 decrease has been associated with the protective effects of olanzapine on methamphetamine-induced neurotoxicity (He et al, 2004).…”

“…Among possible molecules, BDNF is a stronger candidate. It has been shown that chronic administration of olanzapine upregulates the expression of BDNF mRNA in the hippocampus (Bai et al, 2003), and improves memory in different maze tasks in animal studies (Nowakowska et al, 1999;Wolff and Leander, 2003). Indeed, the involvement of BDNF in spatial memory formation and maintenance in a radial arm maze test has been demonstrated in rats (Mizuno et al, 2000;Radecki et al, 2005).…”

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

“…Likewise, potential contributions to weight gain of norepinephrine (Elman et al, 2002(Elman et al, , 2004 and prolactin (Melkersson, 2005;Mann et al, 2006) increases associated with SGA treatment are still unclear. The findings of SGA effects on the brain BDNF (Bai et al, 2003;Luo et al, 2004;Angelucci et al, 2005) and orexin in preclinical literature may be also of potential importance as both neurochemicals are involved in reward and appetitive functions; however, their precise role and how they are influenced by SGAs in humans (Dalal et al, 2003;Weickert et al, 2005) are intriguing topics for future research. In addition, further studies are needed to examine a potential involvement of the endogenous cannabinoid system that has been implicated in schizophrenia (Weiser and Noy, 2005), in obesity (Engeli et al, 2005), and in the mechanisms of action of SGAs, for example, clozapine (Sundram et al, 2005).…”

“…Rank ordering of SGAs' binding affinities argues against antagonism of a single receptor as a sufficient cause for SGA-induced weight gain (Richelson, 1999;Richelson and Souder, 2000). It is possible that simultaneous blockade of H 1 , 5-HT 2 , D 2 , and acetylcholine receptors plays a synergistic role in increased appetite and food intake (Richelson, 1999;Richelson and Souder, 2000) Chemistry Opioidergic activity m (Schreiber et al, 1997;Schreiber et al, 1999;Weizman et al, 2003;O'Malley et al, 1999;Kochhar et al, 2002;Palenzona et al, 2004) SGAs may worsen opioid-mediated food hedonics BDNF m In hippocampus and in PFC (Bai et al, 2003;Angelucci et al, 2005;Luo et al, 2004) Clinical significance of these changes observed in preclinical studies is unknown Orexin K Preclinical study: m in activity in LH K Clinical study: no effect in CSF (Dalal et al, 2003) The preclinical study revealed high degree of specificity for the LH site of orexin effects; such neuroanatomic precision was unattainable with CSF sampling employed in the clinical study…”

Are lectin positive spherical deposits detected in the molecular layer of the hippocampal formation related with neuronal apoptosis?

“…Some experimental studies were reported that a kind of therapeutic products of major tranquillizers induced neuron apoptosis in dentate gyrus (12)(13)(14). As the lectin positive spherical shaped deposits were detected in not only 5 schizophrenia cases (case No.…”