Behavioural brain research
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Substantia nigra (SN) is rich in dopamine (DA)-ergic and GABA-ergic neurons, which project to and receive inputs from locus coeruleus (LC) and pedunculo-pontine tegmentum (PPT) possessing REM-OFF and REM-ON neurons, respectively. Loss of DA-ergic neurons and disturbed REM sleep (REMS) are associated with Parkinson's disease, depression and REMS behavior disorder. GABA-ergic projections from SN act pre-synaptically on the noradrenaline (NA)-ergic terminals coming from the LC-REM-OFF neurons onto the REM-ON neurons in PPT and play a critical role in initiating REMS. ⋯ REMS was decreased and increased by Hal and Bic, respectively; while their co-injection neutralized (ineffective) the individual effects. Combining these findings with previous reports suggest that the SN-DA-ergic neurons act on the SN-GABA-ergic to regulate REMS. The results advance our understanding of the neuro-anatomo-chemical connections and pharmaco-physiological regulation of REMS in health and diseases.
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The number of patients with depressive disorders is increasing. However, the mechanism of depression onsets has not been completely revealed. We previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. ⋯ These depression-like behaviors were restored by fluvoxamine and LY341495 injection prior to these tests. Furthermore, the intracerebral administration of only fluvoxamine, but not of LY341495, to the dorsal striatum and direct infusion of LY341495 to the dorsal raphe also rescued. Taken together, Shati/Nat8l in the striatum has an important role in the vulnerability to depression onsets by regulating the origin of serotonergic neuronal system via GABAergic projection neuron in the dorsal raphe from the dorsal striatum.
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The pharmacological effects of tobacco products are primarily mediated by nicotine; however, research suggests that several non-nicotine tobacco constituents may alter the reinforcing effects of nicotine. This study evaluated the reinforcing effects of aqueous solutions of smoke/aerosol condensate from cigarettes, little cigars, electronic cigarettes (e-cigarettes), and waterpipe tobacco in a self-administration procedure to determine if abuse liability of these tobacco products differed. Adult male Sprague-Dawley rats (n = 64 total) were trained to self-administer intravenous nicotine (30 μg/kg/infusion) on a fixed ratio 5 schedule of reinforcement. ⋯ Smoke/aerosol condensate from all tobacco products produced similar levels of responding compared to nicotine alone during the progressive ratio phase. Results suggest that non-nicotine constituents in cigarettes, little cigars, and e-cigarettes differentially enhance nicotine's reinforcing potency. In contrast, waterpipe tobacco blunted nicotine's reinforcing potency, suggesting that it may contain unique constituents that dampen nicotine's reinforcing effects.
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Mild cognitive impairment (MCI) is inconclusively associated with regional gray matter (GM) abnormalities in Parkinson's disease (PD). We aimed to quantitatively evaluate whole-brain voxel-based morphometry (VBM) studies that have investigated brain GM changes in PD patients with MCI (PD-MCI). Seed-based d Mapping, a well-validated coordinate-based meta-analytic approach, was utilized. ⋯ The most reliable finding identified in this meta-analysis was that patients with PD-MCI exhibited greater GM atrophy in the left anterior insula than those with PD-NCI. Our findings further suggest that several moderators (age, gender, educational level, disease stage, severity of motor disability, and the severity of cognitive impairments) in PD-MCI individuals, as well as scanner field-strength, may drive heterogeneous GM changes across studies. GM abnormalities in the anterior insula, an important cognitive hub involved in switching between neural networks, contribute to understanding the neural substrates of MCI in PD, which may serve as a biomarker of PD-MCI.
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Literature data show diverse vulnerability to the rewarding effects of cocaine in human as well as in laboratory animals. The molecular mechanisms of these differences have not been discovered yet. While the initial effects of cocaine depend primarily on the dopamine system, numerous studies have shown that adaptation within the glutamatergic system is responsible for the development of addiction. ⋯ The results suggest the a lack of NF-κB involvement in the regulation of GLT-1 expression by ceftriaxone in the NAc. Additionally, we are the first to report that ceftriaxone strongly upregulates the GLT-1 in the HIP in a transcriptional mechanism involving the Nf-κB transcription factor. Future experiments may resolve the question concerning whether modulation exclusively of the GLT-1 expression in the HIP may attenuate cocaine-induced place preference or relapse.