Table 1.
Effects of region specific lesions, administration of intracranial injections of pharmacological agents, and optogenetic- or DREADD-based activity manipulations on drug taking and seeking behaviors.
| Brain Region(s) | Cocaine | Methamphetamine | Alcohol | Heroin | Nicotine | Reference(s) |
|---|---|---|---|---|---|---|
| dMPFC, PrL (dorsomedial prefrontal cortex; Prelimbic cortex) | TTX inactivation ↓seeking; optogenetic excitation ↓seeking and optogenetic inhibition ↓seeking | B+M inactivation had no effect on context seeking but ↓ drug+cue seeking | B+M inactivation ↓seeking | B+M inactivation has no effect on seeking | Bossert et al., 2011; Chen et al., 2013; Fuchs et al., 2005; Li et al., 2015; Rocha and Kalivas, 2010; Stefanik et al., 2012; Willcocks and McNally, 2013 | |
| vPFC, IL (dorsolateral prefrontal cortex; Inrfalimbic cortex) | TTX had no effect on seeking | B+M inactivation↓ or had no effect on seeking | B+M inactivation had no effect on seeking | B+M inactivation and Daun02 inactivation ↓seeking | Bossert et al., 2011; Fuchs et al., 2005; Li et al., 2015; Rocha and Kalivas, 2010; Willcocks and McNally, 2013 | |
| OFC (orbitofrontal cortex) | LOFC B+M inactivation ↓seeking | B+M inactivation had no effect on seeking | Lasseter et al., 2009, Li et al., 2015 | |||
| Ins (Insular cortex) | B+M inactivation ↓SA and seeking | Pushparaj et al., 2015 | ||||
| DStr (Dorsal striatum) | DLS M+B inactivation or α-flupenthixol ↓ seeking; CNQX or JNJ16259685 had no effect on seeking | DMS B+M inactivation prevents devalutation early in SA/habit learning; DLS B+M inactivation renew sensitivity to devaluation later in SA/habit learning | SCH23390 ↓seeking; LY379268 had no effect on seeking | Bossert et al., 2006, 2009; Corbit et al., 2012; Fuchs et al., 2006; Murray et al., 2014; Xie et al., 2012 | ||
| NAc core (Nucleus accumbens, core subregion) | optogenetic excitation of D2 MSNs ↓ SA; DREADD inhibition of D2 MSNs ↑SA; optogenetic inhibition, B+M inactivation, JNJ16259685 or CNQX, ↓seeking; DAUN02 inactivation had no effect on seeking | B+M inactivation ↓seeking | B+M inactivation or SCH23390 ↓seeking; high frequency DBS or lesion ↓intake | LY379268 or SCH23390 had no effect on seeking | Bock et al., 2013; Bossert et al., 2007; Cassataro et al., 2014; Chaudhri et al., 2009, 2010; Cruz et al., 2014; Fuchs et al., 2004, 2008; Rocha and Kalivas, 2010; Stefanik et al., 2012 Wilden et al., 2014; Xie et al., 2012 | |
| NAc shell (Nucleus accumbens, shell subregion) | B+M inactivation ↓context-induced seeking; B+M inactivation has no effect on cue-induced seeking | B+M inactivation, CART, CTAP or SCH23390 ↓seeking; ↓seeking | LY379268 or SCH23390 ↓seeking | Bossert et al., 2006, 2007; Chaudhri et al., 2009; Fuchs et al., 2004; Fuchs et al., 2008; Millan and McNally, 2012; Perry and McNally, 2013 | ||
| VP (Ventral pallidum) | lesion ↓seeking | lesion ↓seeking | Hubner and Koob, 1990 | |||
| BLA (Basolateral amygdala) | TTX inactivation ↓seeking | B+M inactivation had no effect on seeking | naloxone methiodide ↓seeking | SB-277011-A ↓seeking; B+M inactivation had no effect on SA | Fuchs et al., 2005; Li et al., 2015; Khaled et al., 2014; Marinelli et al., 2010; Yu and Sharp, 2015 | |
| CeA (Central nucleus of the amygdala) | SCH23390 ↓SA; LY37928 ↓seeking | B+M inactivation ↓seeking | UCN3 and D-Phe-CRF(12-41) ↓SA | Caine et al., 1995; Funk et al., 2006, 2007; Li et al., 2015; Lu et al.., 2007 | ||
| BNST (Bed nucleus of the stria terminalis) | B+M inactivation ↓seeking | LeuPro NPY ↓binge drinking; DREADD-mediated inhibition of CRF + neurons ↓binge drinking | Buffalari and See, 2011; Pleil et al., 2015 | |||
| HIP (Hippocampus) | TTX, AP5, PP2, Ro25-6981, JNJ16259685, and CNQX in dHip ↓seeking; M+B in CA3 or VHip ↓seeking; M+B in pDHip had no effect on seeking | blockade of opioid receptors in dHip had no effect on seeking | B+M inactivation of vSub ↓seeking | Bossert and Stern, 2014; Fuchs et al., 2005; Lasseter et al., 2010; Luo et al., 2011; Marinelli et al., 2010; Xie et al., 2010, 2013, 2014 | ||
| Hab (Habenula) | Lhab high+low combination DBS ↓seeking; Lhab lesion ↑seeking | Lhab lesions ↑SA | Hab lesion has no effect on SA | Lidocaine-induced inactivation mHab ↑SA; SB-277011-A ↓seeking | Fowler et al., 2011; Friedman et al., 2010; Haack et al., 2014; Khaled et al., 2014; Wang et al., 2009 | |
| VTA (Ventral tegmental area) | optogenetic excitation (tonic firing) ↓intake | Bass et al., 2013 | ||||
| LH (Lateral hypothalamus) | B+M inactivation ↓seeking | Marchant et al., 2014 | ||||
| EW (Edinger-westphal nucleus) | lesion ↓drinking | Bachtell et al., 2004 | ||||
| BLA - NAc | asymmetrical disconnection (M+B in BLA; NBQX in NAc shell) ↑seeking | Millan and McNally, 2011; | ||||
| VTA - NAc Core | optogenetic inhibition ↓seeking | Stefanik et al., 2013 | ||||
| mPFC - NAc Core | optogenetic inhibition ↓SA paired with aversive stimulus | Seif et al., 2013 | ||||
| Ins - NAc Core | optogenetic inhibition ↓SA paired with aversive stimulus | Seif et al., 2013 | ||||
| PrL - NAc Core | optogenetic inhibition ↓seeking | Stefanik et al., 2012 | ||||
| IL - NAc Shell | pharmacological inactivation or optogenetic induction of LTD ↑seeking | asymmetrical disconnection ↓seeking | Bossert et al., 2012; LaLumiere et al., 2012; Peters et al., 2009; Ma et al., 2014 |
Black box = manipulation changes drug self-administration or seeking behaviors (where arrow denotes increase or decrease in behavior, and underline denotes additional study showing no effect); Gray box = manipulation has no effect on drug self-administration or seeking; White box = area untested in a similar manner. Abbreviations: B+M, baclofen + muscimol; DREADD, designer receptor exclusively activated by designer drug; MSN, medium spiny neuron; SA, self-administration; TTX, tetrodotoxin.