GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation.

We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The NTS-lateral nucleus reticularis paragigantocellularis (lPGi)-LC pathway was studied by evaluating neural tract tracer deposits in the lPGi. NMDA and GABAergic receptors agonists and antagonists were microinjected into the NTS, followed by pharmacologically induced seizures. The effects of LC neurotoxic lesions caused by DSP-4, followed by NTS-NMDA receptor activation, on both tonic‒clonic seizures and postictal antinociception were also investigated. The NTS is connected to lPGi neurons that send outputs to the LC. Glutamatergic vesicles were found on dendrites and perikarya of GABAergic interneurons in the NTS. Both tonic‒clonic seizures and postictal antinociception are partially dependent on glutamatergic-mediated neurotransmission in the NTS of seizing rats in addition to the integrity of the noradrenergic system since NMDA receptor blockade in the NTS and intrathecal administration of DSP-4 decrease the postictal antinociception. The GABAA receptor activation in the NTS decreases both seizure severity and postictal antinociception. These findings suggest that glutamatergic inputs to NTS-GABAergic interneurons, in addition to ascending and descending noradrenergic pathways from the LC, are critical for the control of both seizures and postictal antinociception.

Effects of bone marrow mononuclear cells on induction of axonal sprouting in cortico-cortical and cortico-striatal pathways in an animal model of cortical ablation.

OBJECTIVES: Many therapies have been proposed in order to investigate the mechanisms of neural repair associated with neurological diseases, including bone marrow mononuclear cells (BMMC) transplantation. However, there is evidence that some encephalic injuries are less responsive to neural repair, such as, for example, cortical ablation. On the other hand, some models of cortical ablation have shown functional recovery after BMMC transplantation. Thus, it is relevant to expand the knowledge of BMMC transplantation-induced neuroplasticity in animal models, considering a promising approach for the rehabilitation of patients with neurological diseases. Using an experimental model of cerebral cortex ablation in adult male Wistar rats, which is known to be poorly responsive to neuroplasticity, the aim of this study was to investigate the effects of BMMC on axonal sprouting in cortico-cortical and cortico-striatal pathways synaptic fields. An anterograde neurotracer was used to evaluate the distribution of axonal fibres. RESULTS: The results showed that BMMC were not able to significantly induce axonal sprouting in the evaluated synaptic fields. Our results reinforced the idea that cortical ablation may be less responsive to neuroplasticity and the beneficial effects of BMMC therapy depend on the particularities of a neural microenvironment intrinsic to a given cortical lesion.

Residual dopamine receptor desensitization following either high- or low-dose sub-chronic prior exposure to the atypical anti-psychotic drug olanzapine.

RATIONALE: Anti-psychotic drugs are antagonists of dopamine D2 receptors and repeated administration may lead to the development of dopamine receptor supersensitivity. OBJECTIVES: The objective of this study is to investigate the effects of sub-chronic olanzapine treatments upon the induction of dopamine receptor supersensitivity. METHODS: Rats were administered ten daily low or high doses of the atypical anti-psychotic drug olanzapine (0.01 or 1.0 mg/kg). After 5 days of withdrawal, all groups received 2.0 mg/kg apomorphine on five successive days. Five days after the apomorphine sensitization protocol, in separate experiments, either a conditioning test or an apomorphine sensitization test was conducted. RESULTS: During the anti-psychotic treatment the high dose of olanzapine induced profound locomotion suppression, whereas the low dose had no effect upon locomotion. The apomorphine treatments given to the vehicle control group generated locomotor sensitization. This sensitization effect was attenuated by the same degree for both the low or high dose prior olanzapine treatments. Also, the low and high-dose olanzapine pre-treatments diminished subsequent apomorphine-conditioned and apomorphine-sensitized locomotor responses. CONCLUSIONS: The equivalent attenuation of the apomorphine sensitization produced by both olanzapine doses indicates that this effect was unrelated to the direct effects of olanzapine upon locomotion. Furthermore, the persistence of the desensitization effects well after the termination of the olanzapine treatments is indicative of a residual desensitization of the dopamine system. These findings are of importance when considering the use of atypical anti-psychotic drugs in the treatment of psychoses and other disorders in which overactivity of the dopamine system is considered a contributory factor.

Post-trial apomorphine at an autoreceptor dose level can eliminate apomorphine conditioning and sensitization: support for the critical role of dopamine in re-consolidation.

Re-exposure to conditioned drug stimuli triggers re-consolidation processes. In the present study post-trial apomorphine treatments were administered in order to interact with the re-consolidation of an apomorphine conditioned/sensitized locomotor response. A low (0.05 mg/kg) and a high (2.0mg/kg) dose were used to inhibit or to enhance dopamine activity, respectively. Initially, groups received 5 daily apomorphine (2.0mg/kg)/vehicle treatments either paired or unpaired to open-field placement. The paired treatments generated a progressive locomotor response. Subsequently, all groups received a 5 min non-drug test for conditioning and a conditioned locomotor response was observed in the paired group. The groups received another apomorphine (2.0mg/kg)/vehicle treatment as a re-induction treatment. At this stage the post-trial protocol was initiated. One set of paired, unpaired and vehicle groups were given a low dose of apomorphine (0.05 mg/kg) post-trial; another set received a high dose of apomorphine (2.0mg/kg) post-trial. The remaining group set received vehicle post-trial. The low dose post-trial treatment eliminated the conditioned and sensitized locomotor response and the high dose post-trial treatment enhanced the conditioned and sensitized locomotor response. The efficacy of the post-trial apomorphine treatments to modify the conditioned and the sensitized response after a brief non-drug exposure to test cues supports the proposition that exteroceptive cues control conditioning and sensitization and that the interoceptive drug cues make little or no associational contribution to apomorphine conditioning and sensitization. In addition, the findings point to the importance of dopamine activation in both the acquisition and re-consolidation of conditioning processes.