- Title
- Cocaine potentiates excitatory drive in the perifornical/lateral hypothalamus
- Creator
- Yeoh, Jiann Wei; James, Morgan H.; Jobling, Philip; Bains, Jaideep S.; Graham, Brett A.; Dayas, Christopher V.
- Relation
- Journal of Physiology Vol. 590, Issue 16, p. 3677-3689
- Publisher Link
- http://dx.doi.org/10.1113/jphysiol.2012.230268
- Publisher
- Wiley-Blackwell Publishing
- Resource Type
- journal article
- Date
- 2012
- Description
- The hypothalamus is a critical controller of homeostatic responses and plays a fundamental role in reward-seeking behaviour. Recently, hypothalamic neurones in the perifornical/lateral hypothalamic area (PF/LHA) have also been implicated in drug-seeking behaviour through projections to extra-hypothalamic sites such as the ventral tegmental area. For example, a population of neurones that expresses the peptide orexin has been strongly implicated in addiction-relevant behaviours. To date, the effect of addictive drugs on synaptic properties in the hypothalamus remains largely unexplored. Previous studies focusing on the PF/LHA neurones, however, have shown that the orexin system exhibits significant plasticity in response to food or sleep restriction. This neuroadaptive ability suggests that PF/LHA neurones could be highly susceptible to modifications by drug exposure. Here, we sought to determine whether cocaine produces synaptic plasticity in PF/LHA neurones. Whole-cell patch-clamp techniques were used to examine the effects of experimenter-administered (passive) or self-administered (SA) cocaine on glutamatergic synaptic transmission in PF/LHA neurones. These experiments demonstrate that both passive and SA cocaine exposure increases miniature excitatory postsynaptic current (mEPSC) frequency in PF/LHA neurones. In addition, SA cocaine reduced the paired-pulse ratio but the AMPA/NMDA ratio of evoked excitatory inputs was unchanged, indicative of a presynaptic locus for synaptic plasticity. Dual-labelling for orexin and excitatory inputs using the vesicular glutamate transporter (VGLUT2), showed that passive cocaine exposure increased VGLUT2-positive appositions onto orexin neurones. Further, a population of recorded neurones that were filled with neurobiotin and immunolabelled for orexin confirmed that increased excitatory drive occurs in this PF/LHA population. Given the importance of the PF/LHA and the orexin system in modulating drug addiction, we suggest that these cocaine-induced excitatory synapse-remodelling events within the hypothalamus may contribute to persistence in drug-seeking behaviour and relapse.
- Subject
- drug-induced synaptic changes; cocaine; drugs of addiction; hypothalamus
- Identifier
- http://hdl.handle.net/1959.13/1052631
- Identifier
- uon:15458
- Identifier
- ISSN:0022-3751
- Rights
- This is the post peer reviewed version of the following article: Yeoh JW, James MH, Jobling P, Bains JS, Graham BA, Dayas CV, 'Cocaine potentiates excitatory drive in the perifornical/lateral hypothalamus', Journal of Physiology, 590(2012), which has been published in final form at http://jp.physoc.org/content/590/16/3677.full
- Language
- eng
- Full Text
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