There is evidence for sex differences in cocaine addiction from both clinical and pre-clinical studies. In particular, pre-clinical studies indicate that females may be more sensitive than males to stress-induced drug-seeking. The dorsal hippocampus (DH) is prominently involved in the stress response, as are the locus coeruleus norepinephrine (LC-NE) and dorsal raphe serotonin (DR 5-HT) systems. Moreover, DH receives strong inputs from LC-NE and DR 5-HT neurons. We hypothesized that the stress associated with non-reinforced drug-seeking during early abstinence (on Extinction Day 1; ED1) may contribute to drug seeking via β-adrenergic and 5-HT neurotransmission in DH. We observed decreased drug-seeking behavior on ED1 following 10 mg/kg S-propranolol (β-adrenergic and 5-HT1A/1B receptor antagonist), R-propranolol (5-HT1A/1B receptor antagonist), or racemic propranolol in both male and female rats. ED1 increased Fos expression in DH, LC, and DR, and DH Fos was decreased by systemic S-propranolol. Based on these results, we investigated the effects of blocking 5-HT and β-adrenoceptor transmission in DH on drug-seeking during ED1 by infusing a cocktail of WAY100635 plus GR127935 (5-HT1A/1B receptor antagonists), betaxolol plus ICI-118,551 (β1 and β2 antagonists), or S-propranolol alone. In males, WAY100635/GR127935 was most effective in reducing drug-seeking on ED1, whereas betaxolol/ICI-118,551 was ineffective. In contrast, S-propranolol was most effective in females in reducing drug-seeking on ED1, and WAY100635/GR127935 and betaxolol/ICI-118,551 were each partially effective. Our results indicate that drug-seeking during initial abstinence involves 5-HT and β-adrenergic signaling in female DH, but only 5-HT signaling in male DH.Neuropsychopharmacology accepted article preview online, 12 August 2016. doi:10.1038/npp.2016.150.
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 March 2021.
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