Lateral hypothalamus is required for context-induced reinstatement of extinguished reward seeking

N. J. Marchant, A.S. Hamlin, G. P. McNally

Research output: Contribution to journalArticle

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Abstract

We studied the role of lateral hypothalamus (LH) in context-induced reinstatement (renewal) of reward seeking. Rats were trained to respond for 4% (v/v) alcoholic beer or 10% (w/v) sucrose reward in one context (Context A) before extinction training in a second context (Context B). On test, rats were returned to the training context, A (ABA), or the extinction context, B (ABB). Return to the training context (ABA) produced robust reinstatement. Reversible inactivation of LH via baclofen/muscimol infusion prevented context-induced reinstatement of beer and sucrose seeking. This prevention was specific to bilateral infusions into LH. We then used the retrograde neuronal tracer cholera toxin b subunit (CTb) combined with detection of the c-Fos protein to identify activated afferents to LH during context-induced reinstatement of beer seeking. Double labeling for c-Fos and CTb revealed a significant recruitment of LH-projecting neurons in nucleus accumbens shell (AcbSh) during reinstatement. These afferents could be classified into two anatomically and functionally distinct groups. First, afferents in the ventral AcbSh projecting to LH were activated during reinstatement. Second, afferents in the dorsomedial AcbSh projecting to LH were activated during test in the extinction context. These recruitments were specific to an AcbSh-LH pathway because they were not observed following CTb injection into the immediately adjacent perifornical hypothalamus. These results show that LH is critical for context-induced reinstatement of reward seeking and that parallel striatal-hypothalamic pathways are recruited following return to the training versus extinction contexts.
Original languageEnglish
Pages (from-to)1331-1342
Number of pages12
JournalJournal of Neuroscience
Volume29
Issue number5
DOIs
Publication statusPublished - Feb 2009

Fingerprint

Lateral Hypothalamic Area
Reward
Cholera Toxin
Sucrose
Proto-Oncogene Proteins c-fos
Corpus Striatum
Muscimol
Baclofen
Nucleus Accumbens
Hypothalamus
Neurons

Cite this

Marchant, N. J. ; Hamlin, A.S. ; McNally, G. P. / Lateral hypothalamus is required for context-induced reinstatement of extinguished reward seeking. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 5. pp. 1331-1342.
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abstract = "We studied the role of lateral hypothalamus (LH) in context-induced reinstatement (renewal) of reward seeking. Rats were trained to respond for 4{\%} (v/v) alcoholic beer or 10{\%} (w/v) sucrose reward in one context (Context A) before extinction training in a second context (Context B). On test, rats were returned to the training context, A (ABA), or the extinction context, B (ABB). Return to the training context (ABA) produced robust reinstatement. Reversible inactivation of LH via baclofen/muscimol infusion prevented context-induced reinstatement of beer and sucrose seeking. This prevention was specific to bilateral infusions into LH. We then used the retrograde neuronal tracer cholera toxin b subunit (CTb) combined with detection of the c-Fos protein to identify activated afferents to LH during context-induced reinstatement of beer seeking. Double labeling for c-Fos and CTb revealed a significant recruitment of LH-projecting neurons in nucleus accumbens shell (AcbSh) during reinstatement. These afferents could be classified into two anatomically and functionally distinct groups. First, afferents in the ventral AcbSh projecting to LH were activated during reinstatement. Second, afferents in the dorsomedial AcbSh projecting to LH were activated during test in the extinction context. These recruitments were specific to an AcbSh-LH pathway because they were not observed following CTb injection into the immediately adjacent perifornical hypothalamus. These results show that LH is critical for context-induced reinstatement of reward seeking and that parallel striatal-hypothalamic pathways are recruited following return to the training versus extinction contexts.",
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Lateral hypothalamus is required for context-induced reinstatement of extinguished reward seeking. / Marchant, N. J.; Hamlin, A.S.; McNally, G. P.

In: Journal of Neuroscience, Vol. 29, No. 5, 02.2009, p. 1331-1342.

Research output: Contribution to journalArticle

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AU - McNally, G. P.

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N2 - We studied the role of lateral hypothalamus (LH) in context-induced reinstatement (renewal) of reward seeking. Rats were trained to respond for 4% (v/v) alcoholic beer or 10% (w/v) sucrose reward in one context (Context A) before extinction training in a second context (Context B). On test, rats were returned to the training context, A (ABA), or the extinction context, B (ABB). Return to the training context (ABA) produced robust reinstatement. Reversible inactivation of LH via baclofen/muscimol infusion prevented context-induced reinstatement of beer and sucrose seeking. This prevention was specific to bilateral infusions into LH. We then used the retrograde neuronal tracer cholera toxin b subunit (CTb) combined with detection of the c-Fos protein to identify activated afferents to LH during context-induced reinstatement of beer seeking. Double labeling for c-Fos and CTb revealed a significant recruitment of LH-projecting neurons in nucleus accumbens shell (AcbSh) during reinstatement. These afferents could be classified into two anatomically and functionally distinct groups. First, afferents in the ventral AcbSh projecting to LH were activated during reinstatement. Second, afferents in the dorsomedial AcbSh projecting to LH were activated during test in the extinction context. These recruitments were specific to an AcbSh-LH pathway because they were not observed following CTb injection into the immediately adjacent perifornical hypothalamus. These results show that LH is critical for context-induced reinstatement of reward seeking and that parallel striatal-hypothalamic pathways are recruited following return to the training versus extinction contexts.

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