Table 3.

Receptor mechanisms underlying Δ⁹-THC’s affective properties.

Assay	Target	Antagonist	Knockout mouse	Results	References
Reward
IVSA	CB1Rs	AM251 SR141716A	N/A	Blocked	Freels et al. (2020, Justinova, Tanda, Redhi, and Goldberg (2003), and Spencer et al. (2018)
CPP	CB1Rs	SR141716A	CB1-KO	Blocked	Braida, Iosue, Pegorini, and Sala (2004), Li et al. (2021)
ICSS	CB1Rs	SR141716A	N/A	Blocked	Katsidoni, Kastellakis, and Panagis (2013)
IVSA	MORs	Naltrexone	N/A	Attenuated	Justinova, Tanda, Munzar, & Goldberg, 2004
CPP	MORs	N/A	MOR-KO	Blocked	Ghozland et al. (2002)
IVSA	A2ARs	MSX-3	N/A	Attenuated	Justinová et al. (2011)
IVSA	Presynaptic A2ARs Postsynaptic A2ARs	SCH-442416 KW-6002	N/A	Attenuated Enhanced	Justinová et al. (2011) and Justinová, Redhi, Goldberg, and Ferré (2014)
IVSA	α7nAChRs	Ro 61-8048	N/A	Attenuated	Justinova et al. (2013)
Aversion
ICSS	CB1Rs	SR141716A	N/A	Blocked	Katsidoni, Kastellakis, and Panagis (2013)
ICSS	CB2Rs	AM630	N/A	Blocked	Spiller et al. (2019)
oICSS	PPARα/PPARγ	GW6471 GW9662	N/A	Attenuated	Hempel et al. (2021)
oICSS CPA	Subcortical glutamate-CB1Rs	N/A	VgluT2-CB1-KO	Attenuated Blocked	Han et al. (2017)
CPA	CB2Rs	N/A	CB2-KO	Blocked	Li et al. (2021)
CPA	Prodynorphin gene	N/A	Dream-KO	Enhanced	Cheng, Laviolette, van der Kooy, and Penninger (2004)
CPA	Prodynorphin gene	N/A	Pdyn-KO	Attenuated	Zimmer et al. (2001))
CPA	KORs	Nor-BNI	KOR-KO	Blocked	Clasen et al. (2017), Ghozland et al. (2002) and Norris, Szkudlarek, Pereira, Rushlow, and Laviolette (2019)
Anxiolytic effect
LDB EPM	CB1Rs	SR141716A	N/A	Blocked	Berrendero and Maldonado (2002) and Rubino et al. (2007)
LDB	MORs DORs	β-funaltrexamine Naltrindole	N/A	Blocked	Berrendero and Maldonado (2002)
EPM	5-HT1ARs	WAY100635	N/A	Blocked	Braida, Limonta, Malabarba, Zani, and Sala (2007)
EPM	5-HT2ARs	N/A	5-HT2AR-KO	Blocked	Viñals et al. (2015)
EPM	CB2Rs	AM630	N/A	Blocked	Ivy et al. (2020)
Anxiogenic effect
EPM	CB1Rs	AM251	N/A	Blocked	Rubino et al. (2008)
EPM	PPARα	GW6471	N/A	Attenuated	Hempel et al. (2021)
EPM Open field	Unknown	CBD	N/A	Attenuated	Liu et al. (2017), Murphy et al. (2017), and Todd and Arnold (2016)

Abbreviations: IVSA—intravenous self-administration, CPP—conditioned place preference, CPA—conditioned place aversion, ICSS—intracranial self-stimulation, oICSS—optical ICSS, LDB—Light dark box, EPM—elevated plus maze, DREAM—downstream regulatory element antagonistic modulator, Pdyn, prodynorphin.