scholarly journals Ethanol-induced conditioned place preference and aversion differentially alter plasticity in the bed nucleus of stria terminalis

2019 ◽  
Author(s):  
Dipanwita Pati ◽  
Melanie M. Pina ◽  
Thomas L. Kash

AbstractContextual cues associated with drugs of abuse, such as ethanol, can trigger craving and drug seeking behavior. Pavlovian procedures, such as place conditioning, have been widely used to study the rewarding/aversive properties of drugs and the association between environmental cues and drug seeking. Previous research has shown that ethanol as an unconditioned stimulus can induce a strong conditioned place preference (CPP) or aversion (CPA) in rodents. However, the neural mechanisms underlying ethanol induced reward and aversion have not been thoroughly investigated. The bed nucleus of the stria terminalis (BNST), an integral part of the extended amygdala, is engaged by both rewarding and aversive stimuli and plays a role in ethanol seeking behavior. Here, we used ex-vivo slice physiology to probe learning-induced synaptic plasticity in the BNST following ethanol-induced CPP and CPA. Male DBA/2J mice (2-3 months old) were conditioned using previously reported ethanol-induced CPP/CPA procedures. Ethanol-induced CPP was associated with increased neuronal excitability in the ventral BNST (vBNST). Conversely, ethanol-induced CPA resulted in a significant decrease in spontaneous glutamatergic transmission without alterations in GABAergic signaling. Ethanol-CPA also led to significant increase in paired pulse ratio at excitatory synapses, suggestive of a decrease in presynaptic glutamate release. Collectively, these data demonstrate that the vBNST is involved in the modulation of contextual learning associated with both the rewarding and the aversive properties of ethanol in mice.

2012 ◽  
Vol 6 ◽  
pp. JEN.S10046 ◽  
Author(s):  
Nobue Kitanaka ◽  
Junichi Kitanaka ◽  
F. Scott Hall ◽  
George R. Uhl ◽  
Kaname Watabe ◽  
...  

The effect of exposure of male mice to a horizontal running wheel (Fast-Trac™) on conditioned place preference (CPP) and hyperlocomotion induced by methamphetamine (METH) was determined. In the first experiment eleven-week-old male ICR mice were divided into three groups and exposed to three different environments (housed individually with (group A) or without a running wheel (group B), or housed in a group of eight mice without a running wheel (group C)) for two weeks except during periods of CPP conditioning and testing procedures. Administration of METH (0.5 mg/kg, i.p.) every other day during three conditioning sessions, with saline conditioning sessions in the other compartment on alternate days (ie, saline/METH conditioning), induced a significant CPP, compared to saline/saline conditioning, in mice of groups A and C, but not B. The increased CPP for METH was significantly attenuated by additional 5-day (drug-free)-exposure to a running wheel in mice of group A (but not group C). In the second experiment, pre-exposure of another set of mice to a running wheel for three days did not affect a subsequent METH (1.0 mg/kg)- or saline-induced horizontal locomotion or rearing, compared with the locomotor activities observed in mice without an experience of a running wheel. These observations suggest that experience of a running wheel may selectively facilitate an attenuation of drug-seeking behavior.


2012 ◽  
pp. S129-S138
Author(s):  
R. ŠLAMBEROVÁ ◽  
M. POMETLOVÁ ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
E. MACÚCHOVÁ ◽  
...  

Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test.


2003 ◽  
Vol 90 (1) ◽  
pp. 405-414 ◽  
Author(s):  
Regula E. Egli ◽  
Danny G. Winder

The bed nucleus of the stria terminalis (BNST) is a structure uniquely positioned to integrate stress information and regulate both stress and reward systems. Consistent with this arrangement, evidence suggests that the BNST, and in particular the noradrenergic input to this structure, is a key component of affective responses to drugs of abuse. We have utilized an in vitro slice preparation from adult mice to determine synaptic and membrane properties of these cells, focusing on the dorsal and ventral subdivisions of the anterolateral BNST (dBNST and vBNST) because of the differential noradrenergic input to these two regions. We find that while resting membrane potential and input resistance are comparable between these subdivisions, excitable properties, including a low-threshold spike (LTS) likely mediated by T-type calcium channels and an Ih-dependent potential, are differentially distributed. Inhibitory and excitatory postsynaptic potentials (IPSPs and EPSPs, respectively) are readily evoked in both dBNST and vBNST. The fast IPSP is predominantly GABAA-receptor mediated and is partially blocked by the AMPA/kainate-receptor antagonist CNQX. In the presence of the GABAA-receptor antagonist picrotoxin, cells in dBNST but not vBNST are more depolarized and have a higher input resistance, suggesting tonic GABAergic inhibition of these cells. The EPSPs elicited in BNST are monosynaptic, exhibit paired pulse facilitation, and contain both an AMPA- and an N-methyl-d-aspartate (NMDA) receptor-mediated component. These data support the hypothesis that neurons of the dorsal and ventral BNST differentially integrate synaptic input, which is likely of behavioral significance. The data also suggest mechanisms by which information may flow through stress and reward circuits.


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