RESUMO
The firing activity of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is an important factor in shaping DA release and its role in motivated behavior. Dendrites in DA neurons are the main postsynaptic compartment and, along with cell body and axon initial segment, contribute to action potential generation and firing pattern. In this study, the organization of the dendritic domain in individual VTA and SNc DA neurons of adult male mice, and their relationship to in vivo spontaneous firing, are described. In comparison with dorsal VTA DA neurons, ventrally located VTA neurons (as measured by cell body location) possess a shorter total dendritic length and simpler dendritic architecture, and exhibit the most irregular in vivo firing patterns among DA neurons. In contrast, for DA neurons in the SNc, the higher irregularity of firing was related to a smaller dendritic domain, as measured by convex hull volumes. However, firing properties were also related to the specific regional distribution of the dendritic tree. Thus, VTA DA neurons with a larger extension of their dendritic tree within the parabrachial pigmented (PBP) nucleus fired more regularly compared with those with relatively more dendrites extending outside the PBP. For DA neurons in the SNc, enhanced firing irregularity was associated with a smaller proportion of dendrites penetrating the substantia nigra pars reticulata. These results suggest that differences in dendritic morphology contribute to the in vivo firing properties of individual DA neurons, and that the existence of region-specific synaptic connectivity rules that shape firing diversity.
Assuntos
Neurônios Dopaminérgicos , Área Tegmentar Ventral , Potenciais de Ação , Animais , Masculino , Camundongos , Substância NegraRESUMO
Not all the people that consume drugs of abuse develop addiction. In this sense, just a percentage of rats express locomotor sensitization after repeated psychostimulant exposure. Neurochemical evidence has shown that locomotor sensitization is associated with changes in dorsolateral striatum (DLS) activity. However, it is unknown if individual differences observed in locomotor sensitization are related to differential neuro-adaptations in DLS activity. In this study, we measured basal dopamine (DA) levels and single unit activity in the DLS of anesthetized rats, after repeated amphetamine (AMPH) administration. Rats were treated with AMPH 1.0â¯mg/kg ip or saline ip for 5â¯days. Following 5â¯days of withdrawal, a challenge dose of AMPH 1.0â¯mg/kg ip was injected. In-vivo microdialysis experiments and single unit recording were carried out twenty-four hours after the last AMPH injection. Sensitized rats showed increased basal DA levels and baseline firing rate of medium spiny neurons (MSNs) compared to non-sensitized rats. The local variation index (Lv) was used to measure the firing pattern of MSNs. In saline rats, a bursty firing pattern was observed in MSNs. A decrease in MSNs baseline Lv accompanies the expression of AMPH locomotor sensitization. Moreover, a decrease in Lv after an acute AMPH 1.0â¯mg/kg injection was only observed in saline and sensitized rats. Our results show individual differences in DLS basal DA levels and firing pattern after repeated AMPH administration, suggesting that an hyperfunction of nigrostriatal pathway, accompanied by a decrease in DLS MSNs firing irregularity underlies the expression of AMPH locomotor sensitization.
Assuntos
Anfetamina/farmacologia , Variação Biológica Individual , Dopamina/metabolismo , Atividade Motora/efeitos dos fármacos , Neostriado/metabolismo , Neostriado/fisiologia , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Individualidade , Masculino , Neostriado/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The repeated administration of amphetamine can lead to locomotor sensitization. Although the repeated administration of amphetamine has been associated with anxiety and impaired working memory, it is uncertain if expression of amphetamine sensitization is associated with modifications of emotional memories. To address this issue, rats were injected once daily with amphetamine for five consecutive days (1.5mg/kg). After four days of withdrawal, rats were delivered an acute amphetamine injection to assess the expression of sensitization. A single exposure to an elevated plus maze (EPM), 24h after the last injection of amphetamine, showed that amphetamine sensitization is not accompanied by anxiety. Next, aversive memory was assessed using an 11day inter-trial interval between the EPM Trial 1 and EPM Trial 2. Rats administered with saline showed a percentage of open arms time (% OAT) in Trial 2 that was comparable to Trial 1, demonstrating a reduction in the retrieval of aversive memory. However, rats sensitized after the EPM Trial 1 showed a significant decrease in the % OAT in Trial 2. Importantly, a decrease in the % OAT in Trial 2 compared to Trial 1 was also observed after a single injection of amphetamine 24h before Trial 2. These results show a facilitation in the retrieval of aversive memory, and suggest that a previous amphetamine injection is enough to produce a protracted activation of neural circuits necessary for the retrieval of aversive memory.
Assuntos
Anfetamina/farmacologia , Ansiedade/psicologia , Estimulantes do Sistema Nervoso Central/farmacologia , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Masculino , Ratos Sprague-DawleyRESUMO
Amphetamine locomotor sensitization is an animal model for the study of addiction and schizophrenia. The antipsychotic clozapine blocks the hyperlocomotion induced by an acute injection of amphetamine, but its effect on locomotor sensitization after repeated amphetamine administration remains unknown. In the present study we investigate the effect of repeated administration of clozapine on the induction and expression of amphetamine locomotor sensitization. We propose that repeated administration of clozapine blocks the induction and expression of amphetamine sensitization. Male Sprague-Dawley rats were classified according to their locomotor response to an acute saline injection in high responder saline (HRS) or low responder saline (LRS). Rats from both groups were injected once daily with amphetamine for 5 consecutive days. Horizontal locomotor activity was measured during 40 min. Four days after the last injection, an acute dose of amphetamine was administered to assess the expression of sensitization. Clozapine was injected once daily for 4 consecutive days before (pre-treatment) or after (treatment) induction of sensitization. Pre-treatment with clozapine significantly decreases both acute amphetamine-induced hyperlocomotion and the induction and expression of amphetamine sensitization only in LRS rats, showing a protracted hypolocomotor effect. On the other hand, clozapine treatment had no effect over locomotor response on the expression of amphetamine sensitization in either LRS or HRS rats. These data suggest that clozapine effect on amphetamine locomotor response depends on individual differences. Also, our results suggest that clozapine pre-treatment attenuates the neuroplasticity underlying amphetamine sensitization, but clozapine treatment is unable to reverse these changes once amphetamine sensitization has been induced.