Prolonged withdrawal from cocaine self-administration affects prefrontal cortex- and basolateral amygdala–nucleus accumbens core circuits but not accumbens GABAergic local interneurons

Anthony Purgianto, Michael E. Weinfeld, Marina Wolf

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Withdrawal from extended-access cocaine self-administration leads to progressive intensification (‘incubation’) of cocaine craving. After prolonged withdrawal (1–2 months), when craving is high, expression of incubation depends on strengthening of excitatory inputs to medium spiny neurons (MSN) of the nucleus accumbens (NAc). These excitatory inputs interact with the intra-NAc GABAergic ‘microcircuit’, composed of MSN axon collaterals and GABAergic interneurons. Here, we investigated whether the increased glutamatergic neurotransmission observed after prolonged withdrawal is accompanied by altered GABAergic neurotransmission, focusing on NAc core. Rats self-administered cocaine or saline (6 hours/day) and then underwent >40 days of withdrawal. First, we investigated parvalbumin positive (PV+) interneurons, GABAergic fast-spiking interneurons that regulate MSN activity. Immunohistochemical studies revealed no significant change in PV signal intensity or the number of PV+ cells in cocaine rats versus saline controls. We then screened PV and other interneuron markers using immunoblotting. We detected no changes in levels of PV, calretinin, calbindin or neuronal nitric oxide synthase. Because expression of these markers is activity dependent, our results suggest no marked changes in interneuron activity. Finally, we utilized local field potential recording, which can detect GABA-mediated alterations at the circuit level, to investigate potential changes in two circuits implicated in cocaine craving: prelimbic prefrontal cortex to NAc core and basolateral amygdala to NAc core. We detected differential adaptations in these circuits, some of which may involve GABA. Overall, our results suggest that alterations in GABA transmission may accompany incubation of cocaine craving, but they are circuit specific and less pronounced than alterations in glutamate transmission.

Original languageEnglish (US)
Pages (from-to)1682-1694
Number of pages13
JournalAddiction Biology
Volume22
Issue number6
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

Fingerprint

Self Administration
Interneurons
Prefrontal Cortex
Cocaine
Nucleus Accumbens
gamma-Aminobutyric Acid
Neurons
Synaptic Transmission
Calbindin 2
Calbindins
Parvalbumins
Nitric Oxide Synthase Type I
Immunoblotting
Axons
Glutamic Acid
Cell Count
Craving

Keywords

  • cocaine self-administration
  • GABA
  • incubation of craving
  • interneurons
  • local field potential recording
  • nucleus accumbens

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

@article{036b0f4014d245a1a40b40be16114328,
title = "Prolonged withdrawal from cocaine self-administration affects prefrontal cortex- and basolateral amygdala–nucleus accumbens core circuits but not accumbens GABAergic local interneurons",
abstract = "Withdrawal from extended-access cocaine self-administration leads to progressive intensification (‘incubation’) of cocaine craving. After prolonged withdrawal (1–2 months), when craving is high, expression of incubation depends on strengthening of excitatory inputs to medium spiny neurons (MSN) of the nucleus accumbens (NAc). These excitatory inputs interact with the intra-NAc GABAergic ‘microcircuit’, composed of MSN axon collaterals and GABAergic interneurons. Here, we investigated whether the increased glutamatergic neurotransmission observed after prolonged withdrawal is accompanied by altered GABAergic neurotransmission, focusing on NAc core. Rats self-administered cocaine or saline (6 hours/day) and then underwent >40 days of withdrawal. First, we investigated parvalbumin positive (PV+) interneurons, GABAergic fast-spiking interneurons that regulate MSN activity. Immunohistochemical studies revealed no significant change in PV signal intensity or the number of PV+ cells in cocaine rats versus saline controls. We then screened PV and other interneuron markers using immunoblotting. We detected no changes in levels of PV, calretinin, calbindin or neuronal nitric oxide synthase. Because expression of these markers is activity dependent, our results suggest no marked changes in interneuron activity. Finally, we utilized local field potential recording, which can detect GABA-mediated alterations at the circuit level, to investigate potential changes in two circuits implicated in cocaine craving: prelimbic prefrontal cortex to NAc core and basolateral amygdala to NAc core. We detected differential adaptations in these circuits, some of which may involve GABA. Overall, our results suggest that alterations in GABA transmission may accompany incubation of cocaine craving, but they are circuit specific and less pronounced than alterations in glutamate transmission.",
keywords = "cocaine self-administration, GABA, incubation of craving, interneurons, local field potential recording, nucleus accumbens",
author = "Anthony Purgianto and Weinfeld, {Michael E.} and Marina Wolf",
year = "2017",
month = "11",
day = "1",
doi = "10.1111/adb.12430",
language = "English (US)",
volume = "22",
pages = "1682--1694",
journal = "Addiction Biology",
issn = "1355-6215",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Prolonged withdrawal from cocaine self-administration affects prefrontal cortex- and basolateral amygdala–nucleus accumbens core circuits but not accumbens GABAergic local interneurons

AU - Purgianto, Anthony

AU - Weinfeld, Michael E.

AU - Wolf, Marina

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Withdrawal from extended-access cocaine self-administration leads to progressive intensification (‘incubation’) of cocaine craving. After prolonged withdrawal (1–2 months), when craving is high, expression of incubation depends on strengthening of excitatory inputs to medium spiny neurons (MSN) of the nucleus accumbens (NAc). These excitatory inputs interact with the intra-NAc GABAergic ‘microcircuit’, composed of MSN axon collaterals and GABAergic interneurons. Here, we investigated whether the increased glutamatergic neurotransmission observed after prolonged withdrawal is accompanied by altered GABAergic neurotransmission, focusing on NAc core. Rats self-administered cocaine or saline (6 hours/day) and then underwent >40 days of withdrawal. First, we investigated parvalbumin positive (PV+) interneurons, GABAergic fast-spiking interneurons that regulate MSN activity. Immunohistochemical studies revealed no significant change in PV signal intensity or the number of PV+ cells in cocaine rats versus saline controls. We then screened PV and other interneuron markers using immunoblotting. We detected no changes in levels of PV, calretinin, calbindin or neuronal nitric oxide synthase. Because expression of these markers is activity dependent, our results suggest no marked changes in interneuron activity. Finally, we utilized local field potential recording, which can detect GABA-mediated alterations at the circuit level, to investigate potential changes in two circuits implicated in cocaine craving: prelimbic prefrontal cortex to NAc core and basolateral amygdala to NAc core. We detected differential adaptations in these circuits, some of which may involve GABA. Overall, our results suggest that alterations in GABA transmission may accompany incubation of cocaine craving, but they are circuit specific and less pronounced than alterations in glutamate transmission.

AB - Withdrawal from extended-access cocaine self-administration leads to progressive intensification (‘incubation’) of cocaine craving. After prolonged withdrawal (1–2 months), when craving is high, expression of incubation depends on strengthening of excitatory inputs to medium spiny neurons (MSN) of the nucleus accumbens (NAc). These excitatory inputs interact with the intra-NAc GABAergic ‘microcircuit’, composed of MSN axon collaterals and GABAergic interneurons. Here, we investigated whether the increased glutamatergic neurotransmission observed after prolonged withdrawal is accompanied by altered GABAergic neurotransmission, focusing on NAc core. Rats self-administered cocaine or saline (6 hours/day) and then underwent >40 days of withdrawal. First, we investigated parvalbumin positive (PV+) interneurons, GABAergic fast-spiking interneurons that regulate MSN activity. Immunohistochemical studies revealed no significant change in PV signal intensity or the number of PV+ cells in cocaine rats versus saline controls. We then screened PV and other interneuron markers using immunoblotting. We detected no changes in levels of PV, calretinin, calbindin or neuronal nitric oxide synthase. Because expression of these markers is activity dependent, our results suggest no marked changes in interneuron activity. Finally, we utilized local field potential recording, which can detect GABA-mediated alterations at the circuit level, to investigate potential changes in two circuits implicated in cocaine craving: prelimbic prefrontal cortex to NAc core and basolateral amygdala to NAc core. We detected differential adaptations in these circuits, some of which may involve GABA. Overall, our results suggest that alterations in GABA transmission may accompany incubation of cocaine craving, but they are circuit specific and less pronounced than alterations in glutamate transmission.

KW - cocaine self-administration

KW - GABA

KW - incubation of craving

KW - interneurons

KW - local field potential recording

KW - nucleus accumbens

UR - http://www.scopus.com/inward/record.url?scp=84979289583&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979289583&partnerID=8YFLogxK

U2 - 10.1111/adb.12430

DO - 10.1111/adb.12430

M3 - Article

VL - 22

SP - 1682

EP - 1694

JO - Addiction Biology

JF - Addiction Biology

SN - 1355-6215

IS - 6

ER -