Table 3. Effects of Previous Cannabinoid Exposure on Drug Self-Administration and Place Conditioning in Rodents.

Study	Subjects	Exposure drug	Exposure regimena	Age during exposure	Drug-free periodb	Test drugc	Age at start of testing	FR1 self-admin.	PR self-admin.	Place conditioningd
Norwood et al (2003)	Lewis rats	CP	0.1→0.2 mg/kg/day for 16 days	Starting at PND 55–56	8 Days	Morphine	11 Weeks	Male ↑
González et al (2003)	Wistar rats	THC	Dams given 5 mg/kg/day PO	Perinatal: GD5 through PND 24	⩾7 Weeks	Morphine …Food	⩾10 Weeks		Female = e Male= … Female = Male =
Gonzalez et al (2004)	Wistar rats	THC	5 mg/kg/day for 7 days	Starting at 8–10 weeks	0 Days	Morphine			Male =
Solinas et al (2004)	S-D rats	THC	2→8 mg/kg twice daily for 3 days	Starting at 10-12 weeks	8 Days	Heroin	12–13 Weeks	Male ↑	Male =
Ellgren et al (2007)	L-E rats	THC	1.5 mg/kg/day, intermittent (8 out of 22 days)	PND 28–49	1 week	Heroin	8 Weeks	Male ↑
Biscaia et al (2008)	Wistar rats	CP	0.4 mg/kg/day for 11 days	PND 35–45		Morphine	10 Weeks	Female = f Male ↑	Female = Male=
Tomasiewicz et al (2012)	L-E rats	THC	1.5 mg/kg/day, intermittent (8 out of 22 days)	PND 28–49	5 Weeks	Heroin	12 Weeks	Male ↑ Male with Penk KD =
Stopponi et al (2014)	Wistar rats	THC	2.5→10 mg/kg twice daily for 11 days	PND 35–45	30 Days	Heroin … Yohimbine reinstatement of heroin seeking	11 Weeks	Male = … Male ↑
Vela et al (1998)	Wistar rats	THC	Dams given 5 mg/kg/day PO	Perinatal: GD5 through PND 1	>11 Weeks	Morphine … Food	>11 Weeks	Female ↑ Male = ... Female = Male =
Spano et al (2007)	L-E rats	THC	Dams given 0.15 mg/kg/day IV	Perinatal: GD5 through PND 2	8 Weeks	Heroin	9 Weeks	Male =/↑g
Morel et al (2009)	L-E rats	THCh	5→10 mg/kg/day, intermittent (10 out of 14 days)	PND 35–48	7–14 Days	Morphinei	9 Weeks	Maternally deprived male ↓j Nondeprived male =		Maternally deprived male ↓ Nondeprived male ↑
Singh et al (2006)	Wistar rats	THC	5 mg/kg/day for 10 days	PND 4–14	1 Week	Heroin	3 Weeks			Male ↑
Cadoni et al (2013)	Lewis rats … Fischer rats	THC	2→8 mg/kg twice daily for 3 days	PND 38–42	30 Days	Heroin	10 Weeks			Lewis male = … Fischer male ↑
Rubio et al (1995)	Wistar rats	THC	Dams given 5 mg/kg/day PO	Perinatal: GD5 through PND 24	>7 Weeks	Morphine	>10 Weeks			Female = k Male ↑
Rubio et al (1998)	Wistar rats	THC	Dams given 1, 5 or 20 mg/kg/day PO	Perinatal: GD5 through PND 24	>7 weeks	Morphine	>10 Weeks			Female ↑l Male ↑
DiNieri et al (2011)	L-E rats	THC	Dams given 0.15 mg/kg/day IV	Perinatal: GD5 through PND 2	8 Weeks	Morphine	9 Weeks			Male ↑
Jardinaud et al (2006)	CD1 mice	THC	10 mg/kg/day for 10 days		15 Days	Morphine				Male ↓
Scherma et al (2016a, 2016b)	Lister-Hooded rats	THC	2.5→10 mg/kg twice daily for 11 days	PND 45–55	15 Days	WIN 55212-2	10 Weeks	Male ↑
Valjent and Maldonado (2000)	CD1 mice	THC	1 Or 5 mg/kg (single injection)		1 Day	THC				Male ↑m
Wakeford et al (2016)	S-D rats	THC	3.2 mg/kg/day, intermittent (8 out of 22 days)	PND 28–50	40 Days	THC	13 Weeks			Male = n
Hempel et al (2016)	S-D rats	THC	3.2 mg/kg/day, intermittent (6 out of 12 days)	PND 71–82	3 Days	THC	12 Weeks			Male = o
Hyatt and Fantegrossi (2014)	NIH Swiss mice	THC	1→100 mg/kg/day, intermittent (5 out of 10 days)	Starting at 8 weeks	2 Days	JWH-018 (CB agonist) … MDMA	10 Weeks			Male ↑p … Male =
Rodriguez-Arias et al (2016)	OF1 mice	WIN	0.1 or 0.5 mg/kg/day for 5 days	PND 27–31	3 Days	MDMA	5 Weeks			Male ↑
Cortright et al (2011)	S-D rats	THC	3 mg/kg/day intermittent (5 out of 13 days)	Adult	10 Days	Amphetamine … Apomorphine		Male = … Male =	Male = … Male ↑
Panlilio et al (2007)	S-D rats	THC	2→8 mg/kg twice daily for 3 days	Starting at 10–14 weeks	8 Days	Cocaine	12–14 Weeks	Male =	Male ↓
Higuera-Matas et al (2008)	Wistar rats	CP	0.4 mg/kg/day for 11 days	PND 28–38	7 Weeks	Cocaine … Food	13 Weeks	Female ↑q Male = … Female = Male =
Rodriguez-Arias et al (2016)	OF1 mice	WIN	0.1 or 0.5 mg/kg/day for 5 days	PND 26–30	3 Days	WIN … Cocaine	PND 34			Male = … Male ↑r
Panlilio et al (2013)	S-D rats	THC	2→8 mg/kg twice daily for 3 days	Starting at 10–12 weeks	8 Days	Nicotine	12–13 Weeks	Male ↑	Male =/↑s
Economidou et al (2007)	Wistar rats	THCt	Dams given 5 mg/kg/day PO	Perinatal: GD 15–PND 9	8 Weeks	Ethanolu	9 Weeks	Male =

Abbreviations: PND, postnatal day; GD, gestational day; FR1, fixed-ratio one; PR, progressive ratio; SA, self-administration; PO, per os; CB, cannabinoid; L-E, Long-Evans; S-D, Sprague-Dawley; Penk KD, knockdown of proenkephalin in nucleus accumbens shell; CP, CP-55,940; WIN, WIN 55212-2; MDMA, (±)-3,4-methylenedioxymethamphetamine.

Symbols: →, dose escalated over days; …, different experiment in same study; ↑, enhanced relative to vehicle-treated controls; ↓, diminished relative to vehicle-treated controls; =, no change relative to vehicle-treated controls.

^aTreatments were intraperitoneal and given every day unless otherwise indicated.

^bTime between last exposure and start of behavioral testing.

^cTest drugs were intraperitoneal for place conditioning and intravenous for self-administration, unless otherwise noted.

^dResults involve conditioned place preference unless otherwise indicated.

^eFemales had high morphine and food intake regardless of exposure treatment.

^fFemales had high morphine intake regardless of exposure treatment.

^gTHC exposure did not affect acquisition of responding, but decreased latency to the first response of the session, increased responding for a low dose of heroin, increased heroin intake when rats were acutely food deprived, and increased responding during extinction.

^hDronabinol.

ⁱOral self-administration of freely available morphine solution.

^jTHC exposure prevented escalation of intake seen in vehicle-treated maternal deprivation group.

^kNonsignificant trend for enhancement.

^lSmaller effect than in males.

^mTHC-exposure potentiated conditioning of place preference when the training dose of THC was low and prevented conditioning of place aversion when the training dose of THC was high.

ⁿCombined taste- and place-conditioning procedure. Place preference did not occur in exposed or nonexposed rats.

^oCombined taste- and place-conditioning procedure. Place preference did not occur in exposed or nonexposed rats.

^pTHC-exposure potentiated conditioning of place preference when the training dose of JWH-018 was low and prevented conditioning of place aversion when the training dose of JWH-018 was high.

^qSelf-administration enhanced during first 7 days (acquisition phase), but not during last 14 days (maintenance phase).

^rWIN exposure enhance cocaine induced place preference in groups classified as high or low novelty-seeking, but place preference was only reinstated (after extinction training) by a priming injection of cocaine in the high novelty-seeking group.

^sTHC exposure did not affect responding in a within-session PR test, but enhanced responding when the FR was increased across sessions.

^tTHC was combined with either 3% ethanol or 4.2% sucrose (as a control condition) in the only source of drinking water.

^uOral self-administration with lever press required for access.