TABLE 4.

Effects of opioids on intracranial self-stimulation

Drug Pharmacologya		Doses	Route	Strain/Species	Sex	ICSS Procedureb		Drug Effectc	Dependent Measure	Reference
Drug Name	Selectivity					Structure	Parameter
		mg/kg
Morphine	Mu	5.25–10.25	s.c.	Rat/male	Male	Free operant		Depression	↓rate	Olds and Travis, 1960
Morphine	Mu	10	s.c.	Albino rat		Free operant		Mixed; tolerance	↑↓rate	Adams et al., 1972
Morphine	Mu	5.0–20	s.c.	Sprague-Dawley rat	Male	Free operant		Mixed; tolerance	↑↓rate	Lorens and Mitchell, 1973
Morphine	Mu	4.0–12	s.c.	CDF rat	Male	Discrete trial	Amplitude	Facilitation	↓CIT	Marcus and Kornetsky, 1974
Morphine	Mu	1.0–14	s.c.	CDF rat	Male	Discrete trial	Amplitude	Mixed; tolerance	↓↑CIT	Esposito and Kornetsky, 1977
Morphine	Mu	1.0–18	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Mixed; tolerance	↑↓rate	Altarifi and Negus, 2011
Morphine	Mu	1.0–10	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Mixed; tolerance	↑↓rate	Altarifi et al., 2012
Morphine	Mu	2.5	i.p.	Long Evans rat	Male	Hybrid	Frequency	Facilitation	↓θ0	Carlezon and Wise, 1993a
Morphine	Mu	1.0–5.6	s.c.	C57BL/6J mouse	Male	Hybrid	Frequency	Facilitation	↓M50	Elmer et al., 2010
Morphine	Mu	1.0–5.6	s.c.	DBA mouse	Male	Hybrid	Frequency	Depression	↑M50	Elmer et al., 2010
Heroin	Mu	5.0	i.p.	Wistar rat	Male	Free operant		Mixed; tolerance		Koob et al., 1975
Methadone	Mu	0.1–5.6	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Mixed; tolerance	↑↓rate	Altarifi et al., 2012
Methadone	Mu	0.32–3.2	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Mixed; tolerance	↑↓rate	Altarifi et al., 2013
Fentanyl	Mu	0.001–0.1	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Mixed	↑↓rate	Altarifi et al., 2012
Fentanyl	Mu	0.001–0.1	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Mixed; tolerance	↑↓rate	Altarifi et al., 2013
Hydrocodone	Mu	0.1–10	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Mixed	↑↓rate	Altarifi et al., 2012
Buprenorphine	Mu	0.001–0.1	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Facilitation	↑rate	Altarifi et al., 2012
Nalbuphine	Mu	0.1–10	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Facilitation	↑rate	Altarifi et al., 2012
Nalbuphine	Mu	0.1–10	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	Mixed; tolerance	↑↓rate	Altarifi et al., 2013
β-Funaltrexamine	Mu	0.32–3.2	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	No effect		Altarifi et al., 2012
Naloxone	Mu	0.1	s.c.	Sprague-Dawley rat	Male	Hybrid	Frequency	No effect		Altarifi et al., 2012
Naloxone	Mu	20	i.p.	Wistar rat	Male	Hybrid	Amplitude	No effect	θ5	Borowski and Kokkinidis, 1992
U-69593	Kappa	0.0625–0.5	i.p.	Sprague-Dawley rat	Male	Hybrid	Frequency	Depression	↑θ0	Todtenkopf et al., 2004
U-69593	Kappa	0.1–0.56	i.p.	Sprague-Dawley rat	Male	Hybrid	Frequency	Depression	↑EF50	Do Carmo et al., 2009
U-69593	Kappa	0.056–0.56	i.p.	Sprague-Dawley rat	Male	Hybrid	Frequency	Depression	↓rate	Negus et al., 2010
U-69593	Kappa	0.56	i.p.	Sprague-Dawley rat	Male	Hybrid	Frequency	Depression	↓rate	Leitl et al., 2014
Salvinorin A	Kappa	0.32–3.2	i.p.	Sprague-Dawley rat	Male	Hybrid	Frequency	Depression	↓rate	Negus et al., 2012a
Salvinorin A	Kappa	0.125–2.0	i.p.	Sprague-Dawley rat	Male	Hybrid	Frequency	Depression	↑θ0	Carlezon et al., 2006
SNC80	Delta	10–56	i.p.	Sprague-Dawley rat	Male	Hybrid	Frequency	Depression	↓rate	Do Carmo et al., 2009
SNC80	Delta	10	i.p.	Sprague-Dawley rat	Male	Hybrid	Frequency	Depression; tolerance	↓rate	Negus et al., 2012b

Rate, response rate; CIT, current-intensity threshold; θ₀, theta-0 threshold; θ₅, amplitude maintaining five responses per minute; M₅₀ or EF₅₀, frequency maintaining 50% maximum rate.

^aOpioid receptor subtype selectivity.

^bFirst column indicates structure of experimental session (see text for details). Second column indicates stimulation parameter under manipulation across trials.

^cMost prominent drug effect on ICSS. Tolerance: tolerance to drug-induced depression of ICSS.