TABLE 1.

Monoamine concentrations and ratios measured from microdissected brain regions for mice from the selected and control lines.

			NE			EPI			DA			DOPAC			5HIAA			5HT			DOPAC/DA			5HIAA/5HT
CeA	Control	Sedentary	18.4 ± 2.84	P Values		0.4 ± 0.07	P Values		20.7 ± 2.08	P Values		7.3 ± 0.70	P Values		14.2 ± 0.82	P Values		28.9 ± 0.93	P Values		0.4 ± 0.03	P Values		0.5 ± 0.02	P Values
	Control	Wheel	14.9 ± 1.11	Wheel	0.26602	0.6 ± 0.20	Wheel	0.12738	21.3 ± 4.65	Wheel	0.55262	7.4 ± 1.17	Wheel	0.64849	13.3 ± 1.44	Wheel	0.65161	28.9 ± 2.01	Wheel	0.97017	0.4 ± 0.03	Wheel	0.77843	0.5 ± 0.03	Wheel	0.77612
	Selected	Sedentary	12.5 ± 1.06	Selection	0.02247	0.5 ± 0.15	Selection	0.51325	22.4 ± 4.69	Selection	0.42842	6.0 ± 0.77	Selection	0.48291	13.2 ± 1.14	Selection	0.56901	29.5 ± 1.18	Selection	0.82497	0.3 ± 0.04	Selection	0.06331	0.4 ± 0.03	Selection	0.55147
	Selected	Wheel	11.7 ± 0.47	Selection × Wheel	0.47976	0.7 ± 0.20	Selection × Wheel	0.74610	28.2 ± 9.42	Selection × Wheel	0.62578	7.1 ± 1.85	Selection × Wheel	0.65311	13.0 ± 1.21	Selection × Wheel	0.78278	29.3 ± 4.32	Selection × Wheel	0.95848	0.3 ± 0.03	Selection × Wheel	0.67090	0.5 ± 0.04	Selection × Wheel	0.41611
NaccSh	Control	Sedentary	2.6 ± 0.25	P Values		0.4 ± 0.06	P Values		327.3 ± 11.89	P Values		48.0 ± 2.13	P Values		10.0 ± 0.32	P Values		16.7 ± 0.54	P Values		0.1 ± 0.01	P Values		0.6 ± 0.02	P Values
	Control	Wheel	2.4 ± 0.31	Wheel	0.66491	0.4 ± 0.06	Wheel	0.92945	318.0 ± 15.20	Wheel	0.14364	48.1 ± 3.89	Wheel	0.77019	8.3 ± 1.05	Wheel	0.43062	14.2 ± 1.85	Wheel	0.91690	0.2 ± 0.01	Wheel	0.31095	0.6 ± 0.08	Wheel	0.66962
	Selected	Sedentary	2.2 ± 0.33	Selection	0.26434	0.6 ± 0.12	Selection	0.41443	330.3 ± 29.13	Selection	0.29997	45.0 ± 2.41	Selection	0.04321	8.6 ± 0.63	Selection	0.00626	15.0 ± 1.02	Selection	0.84490	0.1 ± 0.02	Selection	0.23140	0.6 ± 0.05	Selection	0.08619
	Selected	Wheel	2.5 ± 0.34	Selection × Wheel	0.07014	0.5 ± 0.11	Selection × Wheel	0.97553	329.8 ± 20.16	Selection × Wheel	0.53514	38.7 ± 2.16	Selection × Wheel	0.13487	8.7 ± 0.43	Selection × Wheel	0.32461	14.5 ± 0.93	Selection × Wheel	0.06931	0.1 ± 0.00	Selection × Wheel	0.34556	0.6 ± 0.06	Selection × Wheel	0.22145
dICPu	Control	Sedentary	0.5 ± 0.14	P Values		1.9 ± 0.21	P Values		387.0 ± 10.56	P Values		65.1 ± 4.20	P Values		6.8 ± 0.32	P Values		8.3 ± 0.26	P Values		0.2 ± 0.01	P Values		0.8 ± 0.03	P Values
	Control	Wheel	0.6 ± 0.15	Wheel	0.14141	1.8 ± 0.26	Wheel	0.52215	388.4 ± 16.06	Wheel	0.90538	71.5 ± 3.17	Wheel	0.70368	7.0 ± 0.29	Wheel	0.63515	7.6 ± 0.54	Wheel	0.03604	0.2 ± 0.01	Wheel	0.83981	0.9 ± 0.05	Wheel	0.27553
	Selected	Sedentary	0.5 ± 0.08	Selection	0.30083	2.0 ± 0.21	Selection	0.72055	436.4 ± 15.89	Selection	0.00362	66.7 ± 10.60	Selection	0.26381	6.0 ± 0.46	Selection	0.00354	6.7 ± 0.40	Selection	0.00011	0.2 ± 0.02	Selection	0.00988	0.9 ± 0.10	Selection	0.35958
	Selected	Wheel	1.2 ± 0.51	Selection × Wheel	0.31279	1.8 ± 0.11	Selection × Wheel	0.77354	431.6 ± 14.81	Selection × Wheel	0.82370	55.2 ± 3.21	Selection × Wheel	0.17744	5.5 ± 0.24	Selection × Wheel	0.24913	5.8 ± 0.13	Selection × Wheel	0.78875	0.1 ± 0.01	Selection × Wheel	0.13364	0.9 ± 0.05	Selection × Wheel	0.41081
PVN	Control	Sedentary	49.5 ± 5.58	P Values		1.9 ± 0.34	P Values		6.5 ± 0.68	P Values		4.1 ± 0.28	P Values		13.8 ± 0.71	P Values		25.8 ± 0.87	P Values		0.7 ± 0.05	P Values		0.5 ± 0.02	P Values
	Control	Wheel	58.2 ± 4.05	Wheel	0.10823	1.3 ± 0.15	Wheel	0.00882	5.6 ± 0.77	Wheel	0.58849	3.9 ± 0.50	Wheel	0.20437	13.2 ± 0.61	Wheel	0.64880	24.3 ± 1.05	Wheel	0.61406	0.7 ± 0.08	Wheel	0.86450	0.5 ± 0.02	Wheel	0.33553
	Selected	Sedentary	73.5 ± 7.18	Selection	0.71480	1.6 ± 0.30	Selection	0.14308	5.9 ± 0.81	Selection	0.86969	3.8 ± 0.53	Selection	0.12860	11.7 ± 1.07	Selection	0.26820	24.7 ± 1.18	Selection	0.87955	0.6 ± 0.06	Selection	0.33185	0.5 ± 0.04	Selection	0.20894
	Selected	Wheel	39.6 ± 11.98	Selection × Wheel	0.00964	0.7 ± 0.22	Selection × Wheel	0.55284	5.9 ± 1.42	Selection × Wheel	0.60585	2.9 ± 0.47	Selection × Wheel	0.48386	13.1 ± 1.27	Selection × Wheel	0.30717	25.0 ± 1.23	Selection × Wheel	0.40752	0.6 ± 0.11	Selection × Wheel	0.41989	0.5 ± 0.04	Selection × Wheel	0.56156
NaccC	Control	Sedentary	28.3 ± 3.93	P Values		0.9 ± 0.31	P Values		157.8 ± 7.94	P Values		61.0 ± 2.98	P Values		15.1 ± 0.41	P Values		20.5 ± 1.87	P Values		0.4 ± 0.02	P Values		0.8 ± 0.08	P Values
	Control	Wheel	20.2 ± 2.98	Wheel	0.98581	0.9 ± 0.29	Wheel	0.59156	177.9 ± 10.13	Wheel	0.81404	69.4 ± 5.29	Wheel	0.25511	13.8 ± 1.07	Wheel	0.21841	16.8 ± 2.16	Wheel	0.19327	0.4 ± 0.02	Wheel	0.34431	0.9 ± 0.05	Wheel	0.74380
	Selected	Sedentary	17.8 ± 2.63	Selection	0.66998	0.7 ± 0.29	Selection	0.29511	153.7 ± 10.96	Selection	0.71051	58.3 ± 6.19	Selection	0.03019	12.1 ± 0.50	Selection	0.40815	17.0 ± 1.57	Selection	0.52422	0.4 ± 0.04	Selection	0.08827	0.7 ± 0.07	Selection	0.94692
	Selected	Wheel	22.8 ± 3.61	Selection × Wheel	0.46209	0.7 ± 0.26	Selection × Wheel	0.48449	161.9 ± 7.80	Selection × Wheel	0.82396	52.6 ± 2.79	Selection × Wheel	0.24497	12.3 ± 1.00	Selection × Wheel	0.16940	21.1 ± 2.62	Selection × Wheel	0.41057	0.3 ± 0.02	Selection × Wheel	0.16475	0.6 ± 0.07	Selection × Wheel	0.73834
MeA	Control	Sedentary	12.4 ± 0.40	P Values		1.5 ± 0.33	P Values		0.7 ± 0.17	P Values		1.3 ± 0.18	P Values		8.5 ± 0.33	P Values		12.1 ± 0.49	P Values		3.1 ± 0.97	P Values		0.7 ± 0.04	P Values
	Control	Wheel	14.6 ± 1.91	Wheel	0.04889	1.1 ± 0.46	Wheel	0.90902	1.2 ± 0.28	Wheel	0.04687	1.9 ± 0.14	Wheel	0.10097	8.9 ± 0.63	Wheel	0.09407	11.7 ± 1.22	Wheel	0.89426	2.0 ± 0.41	Wheel	0.29631	0.8 ± 0.11	Wheel	0.58139
	Selected	Sedentary	11.2 ± 0.71	Selection	0.41291	0.7 ± 0.10	Selection	0.20437	0.7 ± 0.23	Selection	0.71431	1.6 ± 0.22	Selection	0.83114	7.1 ± 0.43	Selection	0.07377	10.4 ± 0.51	Selection	0.14980	36.9 ± 31.84	Selection	0.31722	0.7 ± 0.02	Selection	0.13968
	Selected	Wheel	13.9 ± 1.62	Selection × Wheel	0.84608	1.1 ± 0.27	Selection × Wheel	0.26031	1.1 ± 0.30	Selection × Wheel	0.71431	1.7 ± 0.17	Selection × Wheel	0.13816	8.4 ± 0.62	Selection × Wheel	0.33486	13.6 ± 1.47	Selection × Wheel	0.07394	2.3 ± 0.85	Selection × Wheel	0.32558	0.7 ± 0.07	Selection × Wheel	0.33566
CA1	Control	Sedentary	5.1 ± 0.29	P Values		0.4 ± 0.14	P Values		0.2 ± 0.04	P Values		0.2 ± 0.03	P Values		5.7 ± 0.31	P Values		5.4 ± 0.34	P Values		47.9 ± 46.63	P Values		1.1 ± 0.05	P Values
	Control	Wheel	4.5 ± 0.47	Wheel	0.31294	0.4 ± 0.16	Wheel	0.31294	0.2 ± 0.03	Wheel	0.72506	0.3 ± 0.05	Wheel	0.65427	4.8 ± 0.34	Wheel	0.11773	4.6 ± 0.43	Wheel	0.13737	2.4 ± 0.92	Wheel	0.42004	1.1 ± 0.04	Wheel	0.79080
	Selected	Sedentary	6.5 ± 1.96	Selection	0.72967	0.4 ± 0.17	Selection	0.25332	0.2 ± 0.04	Selection	0.41681	0.2 ± 0.05	Selection	0.05929	4.5 ± 0.43	Selection	0.01940	4.6 ± 0.50	Selection	0.14005	1.5 ± 0.49	Selection	0.40164	1.0 ± 0.07	Selection	0.50047
	Selected	Wheel	3.9 ± 0.37	Selection × Wheel	0.38024	0.8 ± 0.24	Selection × Wheel	0.30467	0.2 ± 0.02	Selection × Wheel	0.88446	0.1 ± 0.03	Selection × Wheel	0.04809	4.2 ± 0.27	Selection × Wheel	0.48402	4.1 ± 0.33	Selection × Wheel	0.72602	0.7 ± 0.13	Selection × Wheel	0.43605	1.0 ± 0.07	Selection × Wheel	0.81468
CA3	Control	Sedentary	21.3 ± 1.07	P Values		0.3 ± 0.07	P Values		1.0 ± 0.39	P Values		0.7 ± 0.16	P Values		12.7 ± 0.88	P Values		12.6 ± 2.88	P Values		1.1 ± 0.26	P Values		1.2 ± 0.14	P Values
	Control	Wheel	22.2 ± 2.46	Wheel	0.94964	0.3 ± 0.07	Wheel	0.31978	0.7 ± 0.09	Wheel	0.59752	0.7 ± 0.05	Wheel	0.30480	11.1 ± 0.52	Wheel	0.12047	11.2 ± 1.09	Wheel	0.47981	1.1 ± 0.20	Wheel		1.0 ± 0.06	Wheel	0.56657
	Selected	Sedentary	18.1 ± 1.28	Selection	0.04660	0.4 ± 0.05	Selection	0.31978	0.7 ± 0.20	Selection	0.64701	0.6 ± 0.09	Selection	0.05077	10.2 ± 0.70	Selection	0.01421	10.2 ± 0.69	Selection	0.23667	1.2 ± 0.34	Selection	0.74466	1.0 ± 0.07	Selection	0.52713
	Selected	Wheel	17.0 ± 3.16	Selection × Wheel	0.62358	0.3 ± 0.07	Selection × Wheel	0.37031	0.6 ± 0.13	Selection × Wheel	0.97184	0.4 ± 0.07	Selection × Wheel	0.42178	8.9 ± 1.28	Selection × Wheel	0.83055	8.8 ± 1.60	Selection × Wheel	0.98573	0.8 ± 0.21	Selection × Wheel	0.57338	1.1 ± 0.09	Selection × Wheel	0.35478
dRN	Control	Sedentary	80.0 ± 5.52	P Values		1.3 ± 0.44	P Values		4.7 ± 0.37	P Values		3.8 ± 0.27	P Values		22.0 ± 1.40	P Values		27.6 ± 2.59	P Values		0.8 ± 0.04	P Values		0.8 ± 0.03	P Values
	Control	Wheel	65.4 ± 4.60	Wheel	0.08605	1.3 ± 0.29	Wheel	0.94768	4.3 ± 0.45	Wheel	0.28988	4.0 ± 0.45	Wheel	0.75762	17.5 ± 0.51	Wheel	0.01458	22.9 ± 1.48	Wheel	0.18285	1.0 ± 0.12	Wheel	0.77637	0.8 ± 0.05	Wheel	0.43660
	Selected	Sedentary	57.2 ± 3.93	Selection	0.00261	1.1 ± 0.54	Selection	0.94768	3.0 ± 0.22	Selection	0.00040	2.9 ± 0.22	Selection	0.00507	16.5 ± 0.86	Selection	0.00177	20.8 ± 1.56	Selection	0.02257	1.0 ± 0.09	Selection	0.52060	0.8 ± 0.05	Selection	0.93243
	Selected	Wheel	53.3 ± 5.97	Selection × Wheel	0.31035	1.5 ± 0.40	Selection × Wheel	0.60464	3.2 ± 0.09	Selection × Wheel	0.51763	2.9 ± 0.36	Selection × Wheel	0.88644	15.7 ± 0.64	Selection × Wheel	0.08724	20.1 ± 1.13	Selection × Wheel	0.31807	0.9 ± 0.11	Selection × Wheel	0.21340	0.8 ± 0.03	Selection × Wheel	0.91823
LC	Control	Sedentary	40.7 ± 6.75	P Values		2.8 ± 2.58	P Values		3.7 ± 0.83	P Values		4.9 ± 0.99	P Values		9.8 ± 0.90	P Values		13.6 ± 2.10	P Values		1.6 ± 0.29	P Values		1.3 ± 0.66	P Values
	Control	Wheel	30.3 ± 9.08	Wheel	0.76624	2.0 ± 1.61	Wheel	0.36581	3.2 ± 1.68	Wheel	0.98850	4.1 ± 0.93	Wheel	0.77593	10.2 ± 2.75	Wheel	0.70123	16.6 ± 3.71	Wheel	0.20810	2.2 ± 0.56	Wheel	0.36203	0.6 ± 0.13	Wheel	0.33242
	Selected	Sedentary	38.1 ± 6.60	Selection	0.51888	1.0 ± 0.20	Selection	0.36581	2.7 ± 0.29	Selection	0.55602	3.8 ± 0.50	Selection	0.51059	9.0 ± 0.57	Selection	0.71810	16.2 ± 2.07	Selection	0.26508	1.4 ± 0.08	Selection	0.13336	0.6 ± 0.05	Selection	0.36640
	Selected	Wheel	43.6 ± 10.78	Selection × Wheel	0.33704	0.5 ± 0.29	Selection × Wheel	0.92440	3.1 ± 0.76	Selection × Wheel	0.66812	4.1 ± 0.95	Selection × Wheel	0.56571	9.8 ± 1.88	Selection × Wheel	0.90737	19.9 ± 2.02	Selection × Wheel	0.88748	1.4 ± 0.15	Selection × Wheel	0.37052	0.5 ± 0.08	Selection × Wheel	0.45500
SNc	Control	Sedentary	32.7 ± 4.67	P Values		0.2 ± 0.05	P Values		19.8 ± 2.43	P Values		13.2 ± 1.11	P Values		16.7 ± 0.99	P Values		20.4 ± 1.77	P Values		0.7 ± 0.05	P Values		0.9 ± 0.07	P Values
	Control	Wheel	30.6 ± 2.62	Wheel	0.14792	0.6 ± 0.06	Wheel	0.88565	18.6 ± 1.53	Wheel	0.54463	12.4 ± 0.45	Wheel	0.92175	15.7 ± 0.82	Wheel	0.34229	21.2 ± 1.91	Wheel	0.68829	0.7 ± 0.05	Wheel	0.68353	0.8 ± 0.06	Wheel	0.32381
	Selected	Sedentary	34.9 ± 4.18	Selection	0.67450	0.3 ± 0.09	Selection	0.88565	14.4 ± 0.58	Selection	0.21840	8.1 ± 0.53	Selection	0.00004	12.8 ± 0.83	Selection	0.00028	18.4 ± 1.06	Selection	0.26072	0.6 ± 0.04	Selection	0.00996	0.7 ± 0.05	Selection	0.06740
	Selected	Wheel	25.0 ± 3.10	Selection × Wheel	0.33906	0.5 ± 0.15	Selection × Wheel	0.28901	18.3 ± 3.23	Selection × Wheel	0.27748	9.2 ± 0.68	Selection × Wheel	0.24792	12.1 ± 0.72	Selection × Wheel	0.85462	19.0 ± 2.47	Selection × Wheel	0.95911	0.5 ± 0.06	Selection × Wheel	0.87839	0.7 ± 0.06	Selection × Wheel	0.67043
VTA	Control	Sedentary	29.4 ± 3.88	P Values		1.3 ± 0.35	P Values		28.7 ± 5.06	P Values		19.9 ± 1.90	P Values		16.1 ± 1.15	P Values		22.7 ± 2.18	P Values		0.8 ± 0.09	P Values		0.7 ± 0.06	P Values
	Control	Wheel	27.7 ± 2.11	Wheel	0.12998	2.4 ± 0.42	Wheel	0.83385	30.6 ± 4.37	Wheel	0.09070	21.2 ± 1.98	Wheel	0.11054	15.2 ± 1.46	Wheel	0.65142	20.7 ± 2.40	Wheel	0.68478	0.7 ± 0.05	Wheel	0.86517	0.7 ± 0.03	Wheel	0.21543
	Selected	Sedentary	21.2 ± 1.18	Selection	0.90488	1.6 ± 0.29	Selection	0.83385	11.5 ± 1.91	Selection	0.14631	10.3 ± 1.45	Selection	0.00508	11.7 ± 0.62	Selection	0.82742	19.0 ± 1.42	Selection	0.01001	0.9 ± 0.07	Selection	0.03941	0.6 ± 0.07	Selection	0.32216
	Selected	Wheel	36.9 ± 8.13	Selection × Wheel	0.06298	2.3 ± 0.64	Selection × Wheel	0.68422	30.1 ± 10.20	Selection × Wheel	0.16144	16.6 ± 3.60	Selection × Wheel	0.29554	13.5 ± 0.98	Selection × Wheel	0.20664	23.3 ± 3.56	Selection × Wheel	0.21138	0.8 ± 0.15	Selection × Wheel	0.73663	0.6 ± 0.04	Selection × Wheel	0.56940

Values are presented as means ± SE. P values from two-way ANOVAs for individual brain regions are presented in each cell. pFDR was used to adjust for multiple comparisons, and P values <0.0004 are considered statistically significant and are in inverse color (see Section 5).