Neuronal and glial structural plasticity induced by drugs of abuse

Editorial

15 May 2015

Editorial: structural plasticity induced by drugs of abuse

M. Foster Olive

and

Justin T. Gass

3,843 views

3 citations

Editors

M Foster Olive

Arizona State University

Justin Gass

Medical University of South Carolina

Impact

IL-1β has dual effects on miniature IPSCs in CeA neurons. (A) IL-1β increases mIPSC frequencies in the CeA. (Top) A representative whole- cell voltage clamp recording showing an increase in mIPSC frequency induced by 50 ng/ml IL-1β superfusion. (Bottom) The bar graphs present normalized mIPSC parameters from 62% of CeA neurons (13 of 21 cells) responding to IL-1β with an increase in mIPSC frequency (150.7 ± 10.0% of baseline). mIPSC amplitude (104.0 ± 7.8% of baseline) and kinetics were not significantly changed in these CeA neurons, although some cells showed individual changes in mIPSC amplitude. We calculated statistical significance (∗∗p < 0.01) by t-test. (B) IL-1β decreases mIPSC frequencies and amplitudes in CeA neurons. (Top) Representative recording of a CeA neuron responding to IL-1β with a decrease in mIPSC frequency. (Bottom) Acute application of IL-1β significantly decreased the mIPSC frequency (55.9 ± 9.5% of baseline) and amplitude (76.7 ± 6.2% of baseline) in 29% of CeA neurons (6 of 21 cells). In addition, IL-1β increased the mIPSC rise time (114.3 ± 4.7% of baseline) in these neurons. Statistical significance (*p < 0.05) and (∗∗p < 0.01) were calculated by t-test.

Original Research

19 March 2015

IL-1 interacts with ethanol effects on GABAergic transmission in the mouse central amygdala

Michal Bajo

, 6 more and

Marisa Roberto

Neuroinflammation is hypothesized to enhance alcohol consumption and contribute to the development of alcoholism. GABAergic transmission in the central amygdala (CeA) plays an important role in the transition to alcohol dependence. Therefore, we studied the effects of interleukin-1β (IL-1β), a proinflammatory cytokine mediating ethanol-induced neuroinflammation, and its interaction with ethanol on CeA GABAegic transmission in B6129SF2/J mice. We also assessed ethanol intake in B6129SF2/J mice. Intake with unlimited (24 h) ethanol access was 9.2–12.7 g/kg (3–15% ethanol), while limited (2 h) access produced an intake of 4.1 ± 0.5 g/kg (15% ethanol). In our electrophysiology experiments, we found that recombinant IL-1β (50 and 100 ng/ml) significantly decreased the amplitude of evoked inhibitory postsynaptic potentials (eIPSPs), with no significant effects on paired-pulse facilitation (PPF). IL-1β (50 ng/ml) had dual effects on spontaneous miniature inhibitory postsynaptic currents (mIPSCs): increasing mIPSC frequencies in most CeA neurons, but decreasing both mIPSC frequencies and amplitudes in a few cells. The IL-1β receptor antagonist (IL-1ra; 100 ng/ml) also had dual effects on mIPSCs and prevented the actions of IL-1β on mIPSC frequencies. These results suggest that IL-1β can alter CeA GABAergic transmission at pre- and postsynaptic sites. Ethanol (44 mM) significantly increased eIPSP amplitudes, decreased PPFs, and increased mIPSC frequencies. IL-1β did not alter ethanol’s enhancement of the eIPSP amplitude, but, in IL-1β-responsive neurons, the ethanol effects on mIPSC frequencies were lost. Overall, our data suggest that the IL-1 system is involved in basal GABAergic transmission and that IL-1β interacts with the ethanol-induced facilitation of CeA GABAergic transmission.

5,035 views

52 citations

Experimental Methods. (A) Timeline of the experimental procedure for Experiments 1 and 2. All animals were trained to self-administer food pellets immediately prior to beginning operant alcohol self-administration. VEH, NAC, CEF, and CEFAZ treatment commenced on the last 6–8 days of extinction training. For the NAC experiment, animals were also injected 2 h prior to the test. (B) Timeline of the experimental procedure for Experiment 3. All animals were trained to self-administer food pellets immediately prior to beginning operant alcohol self-administration. VEH, CEF, and CEFAZ treatment commenced on Day 5 of food self-administration and continued through Day 12. (C) Timeline of the procedure for Experiment 4. All animals were trained to self-administer food pellets immediately prior to beginning operant cocaine self-administration. VEH and CEFAZ was administered for the last 6–8 extinction sessions and continued after the cue-primed reinstatement test.

Original Research

10 March 2015

Ceftriaxone and cefazolin attenuate the cue-primed reinstatement of alcohol-seeking

Ana Weiland

, 1 more and

Lori A. Knackstedt

Alcohol consumption and the reinstatement of alcohol-seeking rely on glutamate and GABA transmission. Modulating these neurotransmitters may be a viable treatment strategy to prevent alcohol relapse. N-acetylcysteine (NAC) and the antibiotic ceftriaxone (CEF) alter the glial reuptake and release of glutamate while the antibiotic cefazolin (CEFAZ) modulates GABA signaling without affecting glutamate. Here, we used the extinction-reinstatement model of relapse to test the ability of these compounds to attenuate the reinstatement of alcohol-seeking. Male Sprague-Dawley rats were trained to self-administer 20% (v/v) alcohol in the home cage using an intermittent schedule (24 h on, 24 h off) for 12 sessions. Subsequently, animals self-administered alcohol during daily 45-min operant sessions for 26 sessions, followed by extinction training. We tested whether chronic administration of NAC, CEF, or CEFAZ attenuated the cue-primed reinstatement of alcohol-seeking. CEF and CEFAZ attenuated cue-primed reinstatement of alcohol-seeking while NAC had no effect. We subsequently investigated whether CEF and CEFAZ alter the self-administration of sucrose and chow pellets and if CEFAZ attenuates the reinstatement of cocaine-seeking. The operant self-administration of regular chow and sucrose was not altered by either CEF or CEFAZ. CEFAZ had no effect on cocaine reinstatement, a behavior that has been strongly tied to altered glutamate homeostasis in the nucleus accumbens. Thus the ability of CEFAZ to attenuate alcohol reinstatement likely does not involve the glial modulation of glutamate levels. The dampening of GABA transmission may be a common mechanism of action of cefazolin and ceftriaxone.

5,700 views

39 citations