The distinct roles of various neurotransmitters in modulating methamphetamine-induced conditioned place preference in relevant brain regions in mice

Abstract Methamphetamine (METH) is a highly addictive psychostimulant. Cannabidiol (CBD) is an exogenous cannabinoid without psychostimulating activity, which has potential therapeutic effects on opioid addiction. However, it is unclear whether CBD has therapeutic effects on METH-induced motivational effects. The present study examines whether CBD has a protective effect on METH-induced conditioned place preference (CPP) in rats by regulating the Sigma1R and AKT-GSK3β-CREB signaling pathway. Seventy rats were equally and randomly divided into seven groups. The rat CPP model was established via the intraperitoneal injection (IP) of 2 mg/kg of METH. Next, the intraperitoneal injection of 10, 20, 40, and 80 mg/kg CBD was performed 1 h prior to the injection of saline or METH. The protein expression levels of Sigma1R, AKT, p-AKT, GSK-3β, p-GSK-3β, CREB, and p-CREB in the rats’ prefrontal cortex, nucleus accumbens, and hippocampus and ventral tegmental were detected using western blot analysis. CBD was found to inhibit METH-induced CPP in a dose-dependent fashion. The expression levels of Sigma1R, p-AKT, p-GSK3β, and p-CREB increased significantly in the METH-induced CPP model. Treatment involving different doses of CBD caused differential inhibitory responses in the cellular protein abundance of Sigma1R, p-AKT, p-GSK3β, and p-CREB across various brain regions. The present study found that METH can induce CPP in rats. When a pretreatment of CBD is applied, the CBD can weaken CPP in METH-induced rats by regulating the SigmaR1/AKT/GSK-3β/CREB signaling pathway. The results of this study indicate that CBD has a potential therapeutic effect on METH-induced rewarding effects.

Download Full-text

Conditioned place preference of kisspeptin-10

Reviews on Clinical Pharmacology and Drug Therapy ◽

10.17816/rcf19147-53 ◽

2021 ◽

Vol 19 (1) ◽

pp. 47-53

Author(s):

Ilia Yu. Tissen ◽

Polina A. Chepik ◽

Andrei A. Lebedev ◽

Leila A. Magarramova ◽

Eugenii R. Bychkov ◽

...

Keyword(s):

Conditioned Place Preference ◽

Open Field Test ◽

Physiological Saline ◽

Preference Test ◽

Brain Regions ◽

Place Preference ◽

Male Rats ◽

Plus Maze ◽

Male Wistar Rats ◽

Positive State

INTRODUCTION: Kisspeptins (KISS), a group of brain neuropeptides are involved in sexual behavior. KISS activate the hypothalamic neurons that synthesize gonadotropin releasing hormone. KISS was also detected in the limbic system. Earlier, we showed the activation of sexual motivation after the administration of kisspeptin-10 without increasing the level of testosterone in male rats, which suggests the extrahypothalamic effect of KISS. The aim of this work was to study the possibility of aquisition of conditioned place preference of kisspeptin-10, as well as to study the emotional and investigational behavior in rats after intranasal peptide administration. METHODS: Conditioned place preference test (CPP), open field test (OP) and elevated plus maze (EPM) were used in male Wistar rats. RESULTS: When studying CPP, animals spent 78.6 6.3% of the time in the chamber associated with the administration of KISS compared to control animals with administration of physiological saline (51.2% of the experiment time; p 0.05). After kisspeptin-10 administration locomotor activity was 2-fold increased (p 0.05), and the number of sniffings was 2-fold increased too (p 0.05). The parameters did not significantly differ in animals treated with kisspeptin or saline in PCL. CONCLUSION: Thus repeated intranasal administration of kisspeptin-10 induces the aquisition of CPP in rats. This suggests that kisspeptin-10 can cause activity in the reward system or the activation of brain regions associated with this system, which ultimately leads to the formation of an emotionally positive state.

Download Full-text

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2012.00063 ◽

2012 ◽

Vol 6 ◽

Cited By ~ 26

Author(s):

Rana El Rawas ◽

Sabine Klement ◽

Kai K. Kummer ◽

Michael Fritz ◽

Georg Dechant ◽

...

Keyword(s):

Social Interaction ◽

Conditioned Place Preference ◽

Brain Regions ◽

Place Preference

Download Full-text

α-Conotoxin TxIB: A Uniquely Selective Ligand for α6/α3β2β3 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Conditioned Place Preference in Mice

Marine Drugs ◽

10.3390/md17090490 ◽

2019 ◽

Vol 17 (9) ◽

pp. 490 ◽

Cited By ~ 3

Author(s):

You ◽

Li ◽

Xiong ◽

Zhu ◽

Zhangsun ◽

...

Keyword(s):

Acetylcholine Receptor ◽

Conditioned Place Preference ◽

Nicotinic Acetylcholine Receptor ◽

Addiction Treatment ◽

Brain Regions ◽

Place Preference ◽

Enzyme Linked Immunosorbent Assay ◽

Nicotinic Acetylcholine ◽

Selective Ligand

Abstract: α-Conotoxin TxIB is a specific antagonist of α6/α3β2β3(α6β2*) nicotinic acetylcholine receptor (nAChR) with an IC50 of 28 nM. Previous studies have shown that α6β2* nAChRs are abundantly expressed in midbrain dopaminergic neurons and play an important role in mediating the mechanism of nicotine and other drugs reward effect. It provided important targets for the development of anti-addiction drugs. The present study evaluated the pharmacological activity of TxIB in vivo with conditioned place preference (CPP) model, which were induced by subcutaneous injection (s.c.) of nicotine (NIC, 0.5 mg/kg). α-Conotoxin TxIB inhibited the expression and reinstatement of CPP in mice dose-dependently, but had no significant effect on locomotor activity. The concentrations of dopamine (DA), γ-aminobutyric acid (GABA) and noradrenaline (NE) in different brain regions were measured by enzyme-linked immunosorbent assay (ELISA). We found that TxIB could inhibit the concentrations of DA, GABA and NE in different brain regions (such as nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC)) in NIC-induced mice. The concentrations of DA and NE were decreased in ventral tegmental area (VTA), while GABA had little change. The current work described the inhibition activity of TxIB in NIC-induced CPP, suggesting that α6β2* nAChR-targeted compound may be a promising drug for nicotine addiction treatment.

Download Full-text