Apamin induces plastic changes in hippocampal neurons in senile Sprague-Dawley rats.

Apamin is a neurotoxin extracted from honey bee venom and is a selective blocker of small-conductance Ca²âº-activated K⁺ channels (SK). Several behavioral and electrophysiological studies indicate that SK-blockade by apamin may enhance neuron excitability, synaptic plasticity, and long-term potentiation in the CA1 hippocampal region, and, for that reason, apamin has been proposed as a therapeutic agent in Alzheimer's disease treatment. However, the dendritic morphological mechanisms implied in such enhancement are unknown. In the present work, Golgi-Cox stain protocol and Sholl analysis were used to study the effect of apamin on the dendritic morphology of pyramidal neurons from hippocampus and the prefrontal cortex as well as on the medium spiny neurons from the nucleus accumbens and granule cells from the dentate gyrus (DG) of the hippocampus. We found that only granule cells from the DG and pyramidal neurons from dorsal and ventral hippocampus were altered in senile rats injected with apamin. Our research suggests that apamin may increase the dendritic morphology in the hippocampus, which could be related to the neuronal excitability and synaptic plasticity enhancement induced by apamin.

Neonatal administration of N-omega-nitro-L-arginine induces permanent decrease in NO levels and hyperresponsiveness to locomotor activity by D-amphetamine in postpubertal rats.

Nitric oxide (NO) is associated with dopamine (DA) release. Previously, we demonstrated that rats treated with a non-selective nitric oxide synthase inhibitor, N-omega-nitro-L-arginine (L-NNA) at postnatal days 4-6 (PD4-6) show increased locomotion and disrupt neuronal cytoarchitecture after puberty (PD60). Here, we investigate whether the modulation of NO production in rats at PD4-6 causes long term changes of NO system, its impact on DA innervation, and schizophrenia-like behaviors. NO levels were measured in seven brain areas at PD35, PD60, PD90, and PD120. Autoradiographic studies explored the effect of l-NNA on the expression of D1 and D2 receptors in the caudate-putamen (CPu) and nucleus accumbens (NAcc) at PD60. Locomotor activity was assessed at PD60 using the non-selective DA agonists, amphetamine and apomorphine, and the selective DA receptor agonist [D2, quinpirole; D3, 7-hydroxy-N,N-di-n-propylaminotetralin ((+/-)-7-OH-DPAT)]. L-NNA treatment produced decreases in NO levels in the frontal cortex, striatum, brainstem and cerebellum, while in the occipital cortex changes were observed at PD120. Hippocampus and temporoparietal cortex showed differential levels of NO. Receptor autoradiography revealed increases in D1 receptor levels in the NAcc (shell), while decreases in D2 receptor binding were observed in the CPu and NAcc (core). Amphetamine and quinpirole treatments resulted in increases in locomotion. In contrast, treatment with 7-OH-DPAT produced hypolocomotion at low doses, while increased locomotion was seen at the highest dose. These results show that modulation of NO levels early postnatally (PD4-6) produces long term alteration in NO levels, with possible consequences on DA transmission, and related behaviors relevant to schizophrenia.

Alterations in dendritic morphology of hippocampal neurons in adult rats after neonatal administration of N-omega-nitro-L-arginine.

The dendritic length and dendritic-spine density of the pyramidal neurons of the prefrontal cortex and the CA1 hippocampus of rats using the nonselective nitric oxide synthase inhibitor N-omega-nitro-L-arginine (L-NNA) at different postnatal day (P) periods of the brain development (P1-P3, P4-P6, and P7-P9) were assessed using Golgi-Cox staining after puberty (P60). At P4-P6, the L-NNA treatment produced a significant decrease of the dendritic length and dendritic-spine density of the pyramidal cells of the CA1 hippocampus. In addition, the dendritic length of the pyramidal neurons of the CA1 hippocampus decreased because of the L-NNA treatment at P1-P3. These data suggest that during a specific step in the development of the brain, the nitric oxide levels may play a critical role in the morphological modifications of the pyramidal neurons of the CA1 hippocampus at postpubertal age.