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VTA Lamotrigine microinfusions accelerate the development of cocaine sensitisation
Author(s) -
Vazquez Rafael,
SantosVera Bermary,
ArencibiaAlbite Francisco,
VaquerAlicea Ana,
MariaRios Cristina,
MontielRamos Alan,
DevarieHornedo Marcos,
JimenezRivera Carlos
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb639
Subject(s) - ventral tegmental area , sensitization , pharmacology , dopamine , dopaminergic , behavioral sensitization , anesthesia , saline , lamotrigine , nomifensine , medicine , nucleus accumbens , neuroscience , psychology , epilepsy
Support or Funding Information 2SC1GM084854‐05A1 5R25GM061838‐15 2G12‐RR003051 8G12‐MD007600 Dopaminergic projections arising from ventral tegmental area (VTA) play a key role on drug induced effects in the mesocorticolimbic system. Chronic cocaine administration produces an increased VTA dopamine (DA) cell excitability. VTA DA neurons express a large hyperpolarization activated cation current, known as Ih, that contributes to the electrophysiological properties of neurons in the CNS. We hypothesized that Ih ‐enhances VTA DA cell activity during the development of cocaine sensitization. Cocaine sensitization is the progressive escalation of psychomotor responses that results with repeated cocaine administration. We performed intra VTA microinfusions of Lamotrigine (LTG), an Ih current enhancer. Male Sprague‐Dawley rats (250–300g) were anesthetized and stereotaxically implanted with bilateral 26‐gauge cannulas in the VTA. Animals were divided as following: Vehicle/Saline, LTG/Saline, Vehicle/Cocaine, LTG/Cocaine (microinjections/i.p. injections, respectively). Daily LTG microinjections (0.1ug bilateral) were administered for 7 days. Cocaine treated rats (15 mg/kg, i.p.) were injected 10–15 minutes after the LTG microinfusion. Locomotor activity was recorded for 1 hour every day. On day 8, rats received a first cocaine challenge in the absence of LTG. After a 7 days withdrawal period, a second cocaine challenge was performed. Total ambulatory and stereotype activities were analyzed using One‐Way ANOVA followed by Newman‐Keuls Test. LTG/Cocaine rats showed a significant increase in the acute response to cocaine (p< 0.01). Moreover, these animals developed sensitization two days before the control group. Their locomotor response to cocaine during days 1–3 was significantly higher (p< 0.01) compared to Vehicle/Cocaine rats. However, during cocaine challenge, when no LTG was administered the LTG/Cocaine group's locomotor activity was not significantly different from the Vehicle/Cocaine group. We postulate that LTG in the VTA, acting through the Ih current, enhances neural excitability caused by chronic cocaine administration. Taken together, our data suggest that an enhanced Ih current activity in the VTA may contribute to a greater susceptibility to cocaine neurobiological effect.