Table 1.

Articles on Sex-based Differences in Opioid Effects

Author names	Year	Sample size	Article Type	Primary Outcome Measure	Drug Type	Primary Results
Bodnar et al.	2003	6–11 rats per group (further details not reported)	Experimental	Food Intake	Morphine	Morphine-induced feeding increased in male, but not female rats at low doses, and female, but not male rats at higher doses.
Craft et al.	2006	16–18 female rats; 16–22 male rats (numbers reported were pooled across conditions)	Experimental	Locomotor Activity	Morphine	Morphine relative to saline initially suppressed locomotor activity (an effect most pronounced in males) and later increased locomotor activity for both sexes.
Flores et al.	2003	6 rats per each female/male group	Experimental	Distribution of opioid receptor-like 1 receptor mRNA and co-localization with estrogen receptor mRNA in neurons	N/A	ORL1 –receptor gene abundantly expressed in males/proestrus females; but significantly higher in the rostral trigeminal nucleus caudalis and the junction of the caudalis and interpolaris Vc/Vi of diestrus females
Francisco-DoPrado et al.	1998	6 rats per each female/male group	Experimental	Hyperinsulimenia production	Naloxone and naltrexone	Pretreating concanavalin A-injected rats with naloxone or naltrexone, blocked the hyperinsulinemia produced by the lectin in males as well as females
Harte-Hargrove et al.	2015	73 female rats; 32 male rats	Experimental	Basal transmission, long-term potentiation, mossy fiber transmission	Naloxone	Opioid antagonist naloxone enhanced mossy fiber transmission in females during proestrus, however, no effect was observed in males
Limonta et al.	1991	Minimum of 8 rats per group (further details not reported)	Experimental	MOR-Receptor density	Testosterone	Increase in the number of MOR-receptors was observed in normal females compared to the other groups of rats at day 26; also increased in males between day 26 and 60
Mousavi et al.	2007	Saline and sham females/males (n=4 per group); Intact and gonadectomized females/males (n=8 per group)	Experimental	Glutamate levels in nucleus accumbens	Morphine	Higher glutamate levels in the nucleus accumbens of female morphine tolerant rats; overiectomy decreased the glutamate level; orchidectomy did not change glutamate levels in males
Osada et al.	1991	23 female rats; 22 male rats	Experimental	Hippocampal neuron firing rate, responsiveness to opioid peptides	Opioid neuropeptide	Male rats higher baseline pyramidal cell firing rates than females; neurons of castrated male but not female rats were more responsive to the opioid peptide leu-enkephalin, but not dynorphin
Shishkina et al.	1991	Intact + β-endorphin females and males (n=9 per group); Gonadectomized + β-endorphin (7–8 per group)	Experimental	Gonadal hormone levels, concentration of E2 receptors	Opioid neuropeptide	β-endorphin injections did not change the concentration of estradiol receptors of female rats; reduced the level of estradiol receptors in males. Did not affect serum concentrations of testosterone or estradiol in either male or female rats.
Simerly	1991	4 rats per each female/male group	Experimental	Proenkephalin and prodynorphin mRNA-containing neurons	Testosterone	Adult male rats expressed twice the amount of proenkephalin mRNA containing neurons in the AVPv than female mature rats at baseline.
Stewart & Rodaros	1999	120 female rats; 48 male rats	Experimental	Locomotor activity	Morphine	Intact males (but not orchidectomized males) exhibited progressive increase in morphine-induced locomotor activity; Overiectomized estradiol treated female rats (although not without estradiol) exhibited progressive increases in morphine-induced locomotor activity
Van Kempen et al.	2013	Group 1: 24 female and male mice; Group 2: 38 female and male mice	Experimental	Dynorphin and enkephalin immunoreactivity	N/A	Females had higher levels of dynorphin immunoreactivity in CA3a and enkephalin immunoreactivity in CA3b relative to males
Vodo et al.	2013	4 rats per each female/male group	Experimental	Estrogen receptor, androgen receptor, TRPV1 gene expression	Morphine	Morphine increased estrogen receptor α and estrogen receptor β, as well as the androgen receptor and TRPV1 mRNA expression in the ovary, but not in male teste.
Williams et al.	2011	Minimum of 4 rats per each female/male group	Experimental	Corticotropin-releasing factor, receptor immunoreactivity, density	N/A	Proestrus females expressed increased dual-labeled dendritic profiles and membrane density of corticotropin-releasing factor receptor immunoreactivity relative to males
Williams et al.	2011	Minimum of 5 rats per each female/male group	Experimental	Delta opioid receptor immunoreactivity, density	N/A	Females in proestrus (high estrogen) displayed the lowest level of delta opioid receptor immunoreactivity in the CA1 pyramidal cell layer of all groups.