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. Author manuscript; available in PMC: 2020 Oct 1.
Published in final edited form as: Biol Psychiatry. 2018 Aug 7;85(11):925–935. doi: 10.1016/j.biopsych.2018.07.022

Figure 7.

Figure 7.

Knockdown of orexin in lateral hypothalamus (LH), but not in dorsomedial (DMH)/perifornical (PF), attenuates addiction phenotype. (A) Representative photomicrographs of LH orexin-A-immunoreactive (ir) cells 6 days after injection of control morpholino antisense (Ctrl-AS) (top panel) or orexin morpholino antisense (OX-AS) (bottom panel). Scale bars = 50 μm. (B) Site-specific delivery of OX-AS produced a knockdown in the number of orexin-ir neurons in LH (t10 = 6.140, p = .0001; independent samples t test) without affecting the number of orexin-ir neurons in DMH/PF (p > .05). (C) Sample demand curves of a representative animal before (pretreatment) and after OX-AS treatment in LH. (D) Overall, LH OX-AS treatment resulted in higher demand elasticity (α) values (lower motivation) (t12 = 4.455, p = .0008; paired-samples t test) (left panel). In contrast, LH Ctrl-AS treatment had no effect on α values (p > .05) (right panel). (E) Site-specific delivery of OX-AS decreased the number of DMH/PF orexin-ir neurons (t8 = 2.612, p = .0310; independent samples t test) without affecting LH orexin-expressing neurons (p > .05). (F) DMH/PF OX-AS treatment had no effect on α values (p > .05; paired samples t test) (left panel). Similarly, DMH/PF Ctrl-AS treatment did not affect α values (p > .05; paired samples t test) (right panel). For behavioral testing of both LH and DMH/PF injections, OX-AS, n = 7; Ctrl-AS, n = 6. Error bars are SEM. coc, cocaine; Q0, consumption at null cost; resp, response. *p < .05; ***p < .001.