Effects of 5-HT2AR and 5-HT2CR ligands on the abuse-related behavioral effects of cocaine

The results of studies in which a 5-HT2AR or 5-HT2CR ligand was administered before evaluation of cocaine abuse-related behavioral effects of cocaine assessed in rats or monkeys. “Psychomotor stimulant” effects were evaluated typically in photobeam activity monitors. The “stimulus effects of cocaine” were evaluated in a cocaine versus saline, two-lever discrimination task. In this task, “partial” refers to partial substitution of DOI in a cocaine versus saline discrimination. “Impulsive Action” refers to studies that assayed “action restraint” measures of impulsive action (see text and references). “Reward” refers to studies that evaluated effects of manipulations on intake of cocaine (reinforcing effects) and/or breakpoints (motivational effects) in a cocaine self-administration task. “Cocaine-Seeking” refers to behavioral output reinforced by contextual and/or discrete drug-associated cues during withdrawal or following repeated extinction training that occurred in the absence (“Cue”) or presence of investigator-delivered cocaine (“Cocaine”). The up and down arrows indicate an increase (↑) or decrease (↓), respectively, in the abuse-related behavioral effects of cocaine.

ActionLigandPsychomotor StimulantStimulus Effects of CocaineImpulsive ActionCocaine Self-Administration
5-HT2AR agonistDOIa↑/NEPartialNPNPNP
5-HT2AR antagonistMDL 100907,b SR 463491Bc↓NE
5-HT2CR agonistMK 212,d Ro 60-0175,e WAY 163909,f WAY 161503g
5-HT2CR antagonisthSB242084,i RS102221jNE
  • NE, no effect was observed under the treatment conditions employed; NP, no publications identified for these manipulations.

  • a Evenden, 1998; Evenden and Ryan, 1999; Koskinen et al., 2000; Filip et al., 2004; Blokland et al., 2005.

  • b McMahon and Cunningham, 2001; Fantegrossi et al., 2002; Fletcher et al., 2002, 2011; Winstanely et al., 2003, 2004; Fletcher, 2007; Nic Dhonnchadha et al., 2009; Anastasio et al., 2011; Pockros et al., 2011.

  • c Filip et al., 2004, 2006; Filip, 2005.

  • d Callahan and Cunningham, 1995; Filip and Cunningham, 2003; Filip et al., 2004; Neisewander and Acosta, 2007.

  • e Burbassi and Cervo, 2008; Fletcher et al., 2008, 2011; Grottick et al., 2000; Manvich et al., 2012a.

  • f Navarra et al., 2008; Cunningham et al., 2011, 2013; Anastasio et al., 2014a.

  • g Katsidoni et al., 2011.

  • h SB242084 alone supported self-administration in squirrel monkeys (Manvich et al., 2012b).

  • i Fletcher et al., 2002, 2006, 2008; Winstanely et al., 2003; Frankel and Cunningham, 2004; Neisewander and Acosta, 2007; Burbassi and Cervo, 2008; Manvich et al., 2012b; Pennanen et al., 2013.

  • j Filip and Cunningham, 2003.