Table 1. Opioid agonists.
From left to right, columns indicate the experiment number (Expt, included for ease of referencing specific experimental conditions in the text); the citation for each experiment (Reference); the motivational state under which the animals were tested (Drive); the test diet (Diet); animals’ baseline macronutrient preference (BL pref); notes regarding experimental conditions (Notes; further explanation of select experiments is included in table footnotes); the drug used (Drug), the doses tested (Dose); the site at which the drug was infused (Site); pre-drug, baseline macronutrient intake (Pre, in kcal consumed), broken down into carbohydrate/low fat intake (C), fat/high fat intake (F), and the percent of total consumption due to fat (% F); post-drug intake (Post); and the drug-induced change in intake (Change), broken down into macronutrient components (C and F), the total increase in consumption caused by drug administration (Total), and the percent of that drug-induced increase (ignoring any decreases in intake of individual macronutrient) that could be attributed to increased fat consumption (% F). From top to bottom, experiments are arranged by the pharmacology of the drug tested and the site of administration, and include, respectively, MOR and KOR-specific drugs, and systemic/ICV infusion and site-specific CNS infusions. Abbreviations used in each column are summarized below, again moving from left to right. Drive: AL, ad lib fed; 6 h res, restricted to 6 hours consumption daily, 20 h dep, 20 hour food deprivation. Diet: HF v LF, free choice of high fat (HF) and low fat (LF) diet options presented simultaneously; Macro, free choice of protein, carbohydrate and fat macronutrient options presented simultaneously; HF or LF; high fat and low fat diet intakes assessed in separate experiments. BL pref: C, carbohydrate preferring; F, fat preferring; C=F, fat and carbohydrate equally preferred; C (S5), carbohydrate preferring S5B/Pl rat strain; F (OM), fat preferring Osborne-Mendel rat strain. Drug: DAMGO, [D-Ala2, N-MePhe4, Glyol]-enkephalin; Mor, morphine; Butor, butorphanol; Ketocyc, ketocyclazocine; Dyn A, dynorphin A. Site: 3rd v, third ventricle; Sys, systemic administration; LV, lateral ventricle; NAcc, nucleus accumbens; PVN, paraventricular nucleus. Horizontal lines separate different experimental conditions. Note that for experiments designated HF or LF, animals were not given a choice of macronutrients, but opioid effects on these different diet options were compared in separate experiments. Thus figures presented in the table for these experiments (pre, post and change) represent comparison across groups of animals of the relative magnitude of opioid effects on these diets.
| Pre (kcal) | Post (kcal) | Change (kcal) | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Expt | Reference | Drive | Diet | BL pref | Notes | Drug | Dose | Site | C | F | % F | C | F | % F | C | F | Total ↑ | % F | |
| MOR | 1a | Barnes et al. 2006 | AL | HF v LF | C (S5) | DAMGO | 0.025 μg | 3rd v | 5.0 | 0.0 | 0 | 0.0 | 6.0 | 100 | −5.0 | 6.0 | 6.0 | 100 | |
| 0.25 | 3rd v | 5.0 | 0.0 | 0 | 0.0 | 11.0 | 100 | −5.0 | 11.0 | 11.0 | 100 | ||||||||
| 2.5 | 3rd v | 5.0 | 0.0 | 0 | 0.0 | 9.0 | 100 | −5.0 | 9.0 | 9.0 | 100 | ||||||||
| 1b | F (OM) | DAMGO | 0.25 μg | 3rd v | 0.0 | 6.0 | 100 | 0.0 | 14.0 | 100 | 0.0 | 8.0 | 8.0 | 100 | |||||
| 2.5 | 3rd v | 0.0 | 6.0 | 100 | 0.0 | 30.0 | 100 | 0.0 | 24.0 | 24.0 | 100 | ||||||||
| 2 | Bhakthavatsalam et al. 1986 | AL | macro | Mor | 2.5 mg/kg | Sys | 4.0 | 1.0 | 20 | 6.0 | 2.5 | 29 | 2.0 | 1.5 | 3.5 | 43 | |||
| 3a | Glass et al. 19991 | AL | HF v LF | F=corn oil | Mor | 3 mg/kg | Sys | 2.2 | 1.3 | 37 | 6.3 | 2.9 | 32 | 4.1 | 1.6 | 5.7 | 28 | ||
| 10 | Sys | 2.2 | 1.3 | 37 | 6.2 | 7.1 | 53 | 4.0 | 5.8 | 9.8 | 59 | ||||||||
| 3b | F=lard | Mor | 1 | Sys | 0.0 | 2.8 | 99 | 0.8 | 9.6 | 92 | 0.8 | 6.8 | 7.6 | 90 | |||||
| 3 | Sys | 0.0 | 2.8 | 99 | 1.0 | 14.0 | 93 | 1.0 | 11.2 | 12.2 | 92 | ||||||||
| 10 | Sys | 0.0 | 2.8 | 99 | 0.3 | 21.6 | 99 | 0.3 | 18.8 | 19.1 | 99 | ||||||||
| 3c | F=shortening | Mor | 3 | Sys | 1.8 | 2.6 | 59 | 2.8 | 12.2 | 81 | 1.0 | 9.6 | 10.6 | 91 | |||||
| 10 | Sys | 1.8 | 2.6 | 59 | 2.7 | 19.5 | 88 | 0.9 | 16.9 | 17.8 | 95 | ||||||||
| 4a | Gosnell et al. 1990 | AL | macro | C | Mor | 2 mg/kg | sys | 0.0 | 1.0 | 100 | 5.0 | 2.0 | 29 | 5.0 | 1.0 | 6.0 | 17 | ||
| 10 | sys | 0.0 | 1.0 | 100 | 0.5 | 4.0 | 89 | 0.5 | 3.0 | 3.5 | 86 | ||||||||
| 4b | F | Mor | 2 | sys | 0.0 | 3.0 | 100 | 1.0 | 7.5 | 88 | 1.0 | 4.5 | 5.5 | 82 | |||||
| 10 | sys | 0.0 | 3.0 | 100 | 0.5 | 8.5 | 94 | 0.5 | 5.5 | 6.0 | 92 | ||||||||
| 4c | HF v LF | C | Mor | 2 | Sys | 2.0 | 2.0 | 50 | 7.0 | 3.0 | 30 | 5.0 | 1.0 | 6.0 | 17 | ||||
| 10 | Sys | 2.0 | 2.0 | 50 | 10.0 | 4.0 | 29 | 8.0 | 2.0 | 10.0 | 20 | ||||||||
| 4d | C=F | Mor | 2 | Sys | 1.5 | 6.0 | 80 | 8.0 | 6.0 | 43 | 6.5 | 0.0 | 6.5 | 0 | |||||
| 10 | Sys | 1.5 | 6.0 | 80 | 5.0 | 10.0 | 67 | 3.5 | 4.0 | 7.5 | 53 | ||||||||
| 4e | F | Mor | 2 | Sys | 1.0 | 4.0 | 80 | 3.0 | 10.0 | 77 | 2.0 | 6.0 | 8.0 | 75 | |||||
| 10 | Sys | 1.0 | 4.0 | 80 | 2.0 | 16.0 | 89 | 1.0 | 12.0 | 13.0 | 92 | ||||||||
| 5a | Gosnell et al. 19932 | AL | HF v LF | group 1 | Chronic mor | 2.8 mg/kg/h | Sys | 70.0 | 40.0 | 36 | 20.0 | 65.0 | 76 | −50.0 | 25.0 | 25.0 | 100 | ||
| 5b | group 2 | Chronic mor | 2.8 | Sys | 70.0 | 40.0 | 36 | 30.0 | 75.0 | 71 | −40.0 | 35.0 | 35.0 | 100 | |||||
| 6 | Marks-Kaufman et al. 1980 | 6 h res | macro | Mor | 30 mg/kg | Sys | 25.0 | 25.0 | 50 | 5.0 | 40.0 | 89 | −20.0 | 15.0 | 15.0 | 100 | |||
| 7a | Marks-Kaufman 19823 | 6 h res | macro | Mor | 1 mg/kg | Sys | 40.0 | 35.0 | 47 | 25.0 | 63.0 | 72 | −15.0 | 28.0 | 28.0 | 100 | |||
| 10 | Sys | 40.0 | 35.0 | 47 | 20.0 | 66.0 | 77 | −20.0 | 31.0 | 31.0 | 100 | ||||||||
| 20 | Sys | 40.0 | 35.0 | 47 | 20.0 | 61.0 | 75 | −20.0 | 26.0 | 26.0 | 100 | ||||||||
| 7b | Isocaloric fat | Mor | 10 | Sys | 47.0 | 15.0 | 24 | 35.0 | 20.0 | 36 | −12.0 | 5.0 | 5.0 | 100 | |||||
| 20 | Sys | 47.0 | 15.0 | 24 | 30.0 | 25.0 | 45 | −17.0 | 10.0 | 10.0 | 100 | ||||||||
| 8 | Marks-Kaufman et al. 19904 | 6 h res | macro | Chronic mor | 10 mg/kg/d | Sys | 20.0 | 20.0 | 50 | 10.0 | 30.0 | 75 | −10.0 | 10.0 | 10.0 | 100 | |||
| 9 | Ottaviani et al. 19845 | 6 h res | macro | Chronic mor | 10 mg/kg/d | Sys | 11.0 | 21.0 | 66 | 13.0 | 30.0 | 70 | 2.0 | 9.0 | 11.0 | 82 | |||
| 10a | Shor-Posner et al. 19866 | 6 h res | macro | Light phase | Mor | 2 mg/kg | Sys | 28.3 | 65.6 | 70 | 11.0 | 59.5 | 84 | −17.3 | −6.1 | - | |||
| 10b | Dark phase | Mor | 2 | Sys | 13.2 | 46.4 | 78 | 3.7 | 66.5 | 95 | −9.5 | 20.1 | 20.1 | 100 | |||||
| 10c | AL | macro | Light phase | Mor | 2 | Sys | 2.5 | 2.0 | 44 | 5.0 | 5.0 | 50 | 2.5 | 3.0 | 5.5 | 55 | |||
| 10d | Dark phase | Mor | 2 | Sys | 4.0 | 8.0 | 67 | 7.0 | 12.0 | 63 | 3.0 | 4.0 | 7.0 | 57 | |||||
| 11a | Welch et al. 19947 | AL | HF v LF | Mor | 5 mg/kg | Sys | 75% | 25% | 25 | 32% | 68% | 68 | −43% | 43% | 43% | 100 | |||
| 11b | macro | Mor | 5 | Sys | 40% | 30% | 43 | 25% | 50% | 67 | −15% | 20% | 20% | 100 | |||||
| KOR | 12a | Ookuma et al. 1997 | AL | HF v LF | U50 | 215 nmol | LV | 2.5 | 0.5 | 17 | 3.0 | 11.0 | 79 | 0.5 | 10.5 | 11.0 | 95 | ||
| 12b | 20 h dep | HF v LF | U50 | 215 | LV | 9.0 | 21.0 | 70 | 13.0 | 32.0 | 71 | 4.0 | 11.0 | 15.0 | 73 | ||||
| 13a | Ookuma et al. 1998 | AL | HF v LF | F (OM) | U50 | 22 nmol | 3rd v | 2.0 | 3.0 | 60 | 5.0 | 12.0 | 71 | 3.0 | 9.0 | 12.0 | 75 | ||
| 13b | C (S5) | U50 | 22 | 3rd v | 1.0 | 1.0 | 50 | 7.5 | 7.5 | 50 | 6.5 | 6.5 | 13.0 | 50 | |||||
| 14a | Romsos et al. 19878 | AL | HF v LF | Butor | 0.5 mg/kg | Sys | 0.5 | 0.5 | 50 | 2.0 | 8.0 | 80 | 1.5 | 7.5 | 9.0 | 83 | |||
| 1 | Sys | 0.5 | 0.5 | 50 | 3.0 | 3.0 | 50 | 2.5 | 2.5 | 5.0 | 50 | ||||||||
| 10 | Sys | 0.5 | 0.5 | 50 | 7.5 | 12.5 | 63 | 7.0 | 12.0 | 19.0 | 63 | ||||||||
| 14b | HF or LF | Butor | 1 mg/kg | Sys | 6.0 | 2.0 | 25 | 14.0 | 14.0 | 50 | 8.0 | 12.0 | 20.0 | 60 | |||||
| 10 | Sys | 6.0 | 2.0 | 25 | 19.0 | 29.0 | 60 | 13.0 | 27.0 | 40.0 | 68 | ||||||||
| 14c | Chronic butor | 10 mg/kg/d | Sys | 6.0 | 4.0 | 40 | 17.0 | 31.0 | 65 | 11.0 | 27.0 | 38.0 | 71 | ||||||
| 14d | Ketocyc | 1 mg/kg | Sys | 6.0 | 1.0 | 14 | 6.0 | 12.0 | 67 | 0.0 | 11.0 | 11.0 | 100 | ||||||
| 10 | Sys | 6.0 | 1.0 | 14 | 7.0 | 14.0 | 67 | 1.0 | 13.0 | 14.0 | 93 | ||||||||
| Site-specific infusions | |||||||||||||||||||
| MOR | 15a | Zhang et al. 1998 | AL | HF or LF | DAMGO | 0.25 μg | NAcc | 15.0 | 30.0 | 67 | 35.0 | 100.0 | 74 | 20.0 | 70.0 | 90.0 | 78 | ||
| 2.5 | NAcc | 15.0 | 30.0 | 67 | 35.0 | 125.0 | 78 | 20.0 | 95.0 | 115.0 | 83 | ||||||||
| 15b | HF vs LF | C | DAMGO | 0.25 μg | NAcc | 20.0 | 20.0 | 50 | 25.0 | 45.0 | 64 | 5.0 | 25.0 | 30.0 | 83 | ||||
| 2.5 | NAcc | 20.0 | 20.0 | 50 | 20.0 | 70.0 | 78 | 0.0 | 50.0 | 50.0 | 100 | ||||||||
| 15c | F | DAMGO | 0.25 μg | NAcc | 15.0 | 40.0 | 73 | 10.0 | 70.0 | 88 | −5.0 | 30.0 | 30.0 | 100 | |||||
| 2.5 | NAcc | 15.0 | 40.0 | 73 | 5.0 | 150.0 | 97 | −10.0 | 110.0 | 110.0 | 100 | ||||||||
| 15d | 24 h dep | HF vs LF | DAMGO | 0.25 μg | NAcc | 28.0 | 33.0 | 54 | 23.0 | 70.0 | 75 | −5.0 | 37.0 | 37.0 | 100 | ||||
| 16 | Leibowitz 1999 | 6 h res | macro | DAMGO | 3 nmol | PVN | 5.0 | 2.0 | 29 | 3.5 | 10.0 | 74 | −1.5 | 8.0 | 8.0 | 100 | |||
| 17a | Naleid et al. 20079 | AL | HF vs LF | F | DAMGO | 0.25 nmol | PVN | 17.0 | 40.0 | 70 | 11.0 | 56.0 | 84 | −6.0 | 16.0 | 16.0 | 100 | ||
| 2.5 | PVN | 17.0 | 40.0 | 70 | 9.0 | 72.0 | 89 | −8.0 | 32.0 | 32.0 | 100 | ||||||||
| 17b | C | DAMGO | 0.25 nmol | PVN | 41.0 | 17.0 | 29 | 39.0 | 20.0 | 34 | −2.0 | 3.0 | 3.0 | 100 | |||||
| 2.5 | PVN | 41.0 | 17.0 | 29 | 33.0 | 25.0 | 43 | −8.0 | 8.0 | 8.0 | 100 | ||||||||
| KOR | 18 | Leibowitz 1999 | 6 h res | macro | Dyn A | 3 nmol | PVN | 5.0 | 2.0 | 29 | 2.0 | 7.0 | 78 | −3.0 | 5.0 | 5.0 | 100 | ||
High fat vs. low fat intake was measured using three different fat sources: corn oil, lard, or vegetable shortening.
Rats were divided into three groups in this experiment: a control group never administered drug; a group administered saline continuously for one week through minipump infusion, followed by a second week of continuous morphine infusion (Group 1 in Notes column); and a group in which drugs were administered in the opposite order - morphine first followed by saline (Group 2). For this experiment, baseline macronutrient preference was calculated from the control (never injected) group’s intake averaged over the first week. Drug effects were calculated from macronutrient intake on first post-drug day only.
Two experiments were performed in which rat self-selected macronutrients after morphine injection. In the first experiment the fat component was 7.8 kcal/g; in the second, it was 3.8 kcal/g, isocaloric to the protein and carbohydrate rations. In both experiments, morphine doses (0, 1, 10, 20 mg/kg) were administered in two rounds of injection. Only data from the second round is included here, as the first round had no significant effects on intake.
Morphine was injected daily for 10 days. Baseline intake for this experiment was calculated from the average intake over the five days preceding injection. Drug effects were calculated from last 5 days of morphine injection, the interval over which drug effects differed significantly from control values.
Morphine was injected daily for 22 days. Drug effects on macronutrient intake were calculated from the mean intake over the 5 days of injection, the interval over which there was a statistically significant difference from vehicle injected control rats. Baseline macronutrient preference was calculated from mean intake of control animals during this period.
Morphine effects on diet preference were assessed either during light or dark phase, as indicated in the Notes column.
The authors measured baseline preference by averaging macronutrient intake over 3 days preceding drug treatments, and expressed these preferences as the percent of total caloric intake. To be consistent with baseline measures, drug effects on macronutrient intake (reported in kcal) were converted to percent of total intake in the test session. Thus, all measures for this experiment are reported in Table 1 as percentages of total consumption.
In one experiment (14c), butorphanol was chronically administered (once/day for four days). Data shown are those following only the first day of injection.
The authors provided measures of total intake (kcal) as well as intake difference (fat kcal – sucrose kcal). Raw measures of macronutrient intake were derived algebraically from these values.