Drug addiction is closely related to the dysregulation of complex neural circuits. However, the neural connections underlying the symptoms of methamphetamine (METH)-induced addiction have yet to be elucidated.

METHODS:

We conducted ΔFosB (Delta FBJ murine osteosarcoma viral oncogene homolog B) associated immunofluorescence and electrophysiological recording experiments to measure neural activity of paraventricular thalamus (PVT) neurons in METH treated mice. Then, the METH-mediated conditional place preference (CPP) behaviors were evaluated after chemogenetic manipulation of PVT neurons. Additionally, the neural projection from PVT to medial prefrontal cortex (mPFC) was verified through Adeno-associated virus (AAV) mediating neural tracing method, and its role on METH-mediated CPP behaviors was determined using chemogenetic and neural ablation strategies.

RESULTS:

We found that glutamatergic neurons in PVT were activated by METH. Activating the glutamatergic neurons in PVT promoted the METH-mediated CPP behaviors, while inhibiting these neurons attenuated the CPP behaviors. Moreover, we observed PVT neurons showed robust neuronal projections to mPFC, activation of the mPFC→projecting neurons in PVT or the afferent terminals in mPFC derived from PVT enhanced METH-mediated CPP performance, and ablating the mPFC neurons receipting neural projection from PVT impeded the METH-mediated CPP phenotype.

LIMITATIONS:

The underlying molecular mechanism of the dysfunctional PVT neurons after METH treatment and the PVT neurons regulating the activity of mPFC target neurons remains unclear.

CONCLUSIONS:

These results shed light on that PVT is a key METH addiction-controlling nucleus, and PVT → mPFC projection regulated METH-mediated CPP behavior, which could serve as a vital pathway for morbidity and treatment for METH-mediated addiction.

2025-02-01·NEUROCHEMICAL RESEARCH

Cannabidiol Plays a Modulatory Function on the Methamphetamine-Induced Reward Through Hippocampal D2-Like Dopamine Receptors

Article

作者: Azizbeigi, Ronak ; Haghparast, Abbas ; Omidiani, Seyed Erfan ; Mohammadi, Mahsa

Methamphetamine (METH), a stimulant that is extremely addictive, directly affects the central nervous system. METH's abuse and consumption are directly linked to mental illnesses, psychosis, and behavioral and cognitive impairments. It may disrupt the reward system and dopaminergic transmission. METH's rewarding qualities are associated with a rise in dopamine. Additionally, cannabidiol (CBD), one of the primary cannabinoid components of the cannabis plant, significantly affects dopaminergic transmission and may aid in reward- and addiction-related behaviors. To shed light on the role of the D2-like dopamine receptor (D2R) in the hippocampal dentate gyrus (DG), the present study examined the effects of CBD on the acquisition and expression of the conditioned place preference (CPP) induced by METH. The function of D2R was ascertained by delivering Sulpiride microinjections, as a D2R antagonist Sulpiride (0.25, 1, and 4 μg/0.5 μL DMSO12%) into the DG. Moreover, an intracerebroventricular injection of CBD at a dose of 10 μg/5 μL for CPP acquisition and 50 μg/5 μL for CPP expression was given to rats. According to the current research, CBD dramatically reduced the acquisition and expression of CPP resulting from METH. However, Sulpiride suppressed the effect of CBD on METH-induced CPP acquisition and expression, with a greater impact on expression experiments. Ultimately, this study proposed that the expression experiment of METH-induced CPP appears to be heavily dependent on D2R in the DG.

2025-01-01·NEUROSCIENCE LETTERS

Cannabinoid receptor type 1 agonist disrupts methamphetamine-induced conditioned place preference in adolescent male rats

Article

作者: Shabani, Mohammad ; Ramshini, Effat

Addiction can be viewed as a state of compulsive engagement in drug use. It is believed that drug-associated memories maintain compulsive drug-seeking behavior. Therefore, disrupting drug-associated memories may reduce drug-seeking behavior. In the present study, a conditioned place preference (CPP) apparatus was conducted to evaluate the effect of cannabinoid receptor type 1 (CB1R) agonist and antagonist on the acquisition of CPP induced by methamphetamine (METH). Anxiety behaviors and memory retrieval were assessed using elevated plus maze (EPM) and step-through passive avoidance tasks. In this study using a 5-day schedule of CPP, exposure to METH increased the time spent in the drug-paired compartment, and CB1Rs agonist (WIN 55,212-2, WIN) disrupted the METH-induced CPP. In the EPM experiment, METH significantly decreased the ratio of times spent in the open arms to total times spent in any arms (OAT) and the ratio of entries into open arms to total entries (OAE), indicating that METH increases anxiety-like behaviors. However, the CB1Rs antagonist (SR141716A, SR) reversed METH-induced anxiety behaviors. The results obtained in the passive avoidance experiment showed that blockade of brain CB1Rs by SR improves METH-induced amnesia. In summary, CB1Rs appear to modulate METH-associated memories, and antagonists of CB1Rs may serve as a therapeutic target for METH-induced anxiety behaviors.

100 项与 METH vaccine 相关的药物交易

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