Fig 1.
Dose Response Curves for Agonist-Induced Behavioral Response.
The D2 agonist, quinpirole, stimulates greater locomotor (A) and stereotypic (B) behavior in adolescents (P32) than adults (P90). The selective D1[Gs] agonist, SKF83822, stimulates more locomotor (C) and stereotypic (D) behavior in adults than adolescents. While there are no significant age differences locomotor response to the selective D1[Gq] agonist, SKF83959 (E), 3.0mg/kg SKF83959 stimulates more stereotypy in adolescents than adults (F). Significant age difference, *p<0.05, **p<0.01; n = 6–8 per group.
Fig 2.
Age Differences in Behavioral Synergy.
(A) Locomotor and stereotypic response to quinpirole and SKF83822, alone and in combination (D2 (0.2) + D1[Gs]). (B) Locomotor and stereotypic response to quinpirole and SKF83959, alone and in combination (D2 (0.2) + D1[Gq]). ***p<0.001 vs. saline and additive doses of each agonist along at the same age. +p<0.05 vs. saline, ++p<0.01; n = 10–19 per group
Fig 3.
Age Differences in BNST IEG Synergy.
(A) Cfos expression in the BNST of animals treated with saline, agonist alone, or in combination (B) Arc expression in the BNST of animals treated with saline, agonist alone, or in combination ***p<0.001 vs. saline and additive doses of each agonist along at the same age. +p<0.05 vs. saline, ++p<0.01; n = 6–7 per group
Fig 4.
Baseline Cfos and Arc Networks.
Nodes represent brain regions and are presented in pseudoanatomical space. Edges are lines connecting two nodes, and represent significant r values (p<0.05, n = 6–7), in which thicker lines correspond to more robust r values. Positive and negative r values are depicted with black and red lines, respectively. Colors outlining nodes denote modularity, in which nodes that share the same border color participate in the same sub-community. (A) Cfos networks in saline-injected adolescent controls exhibit local coordinated gene expression (CGE) in the cortex and striatum. (B) Adult baseline cfos networks are sparser than adolescent networks, and functional communities are comprised of more anatomically distributed nuclei. (C) Adolescent baseline arc networks are characterized by functional communities predominately comprised of nuclei that are anatomically proximal to each other, particularly in the cortex. (D) Adult baseline arc networks show a smaller number of functional interrelationships than adolescent networks, but demonstrate unique corticoaccumbens CGE.
Fig 5.
D1/D2-Induced Cfos Network Changes.
Difference maps visually represent significant differences between baseline networks in saline-injected controls and that in animals injected with D1/D2 drug combinations. Nodes represent brain regions and are presented in pseudoanatomical space. Lines indicate functional relationships between nodes that are significantly altered by D1/D2 treatment relative to controls (p<0.01, n = 6–7). Solid black lines indicate gain of a positive cfos CGE. Dashed black lines indicate loss of positive cfos CGE. Solid red lines indicate gain of negative cfos CGE. Dashed red lines indicate loss of negative CGE. (A) Effects of D2 stimulation in adolescents. (B) Effects of D2 stimulation in adults. (C) D1[Gs]/D2 combination treatment in adolescents. (D) Effects of D1[Gs]/D2 combination treatment in adults. (E) Effects of D1[Gq]/D2 combination treatment in adolescents. (F) Effects of D1[Gq]/D2 combination treatment in adults.
Fig 6.
D1/D2-Induced Arc Network Changes.
Difference maps visually represent significant differences between baseline networks in saline-injected controls and that in animals injected with D1/D2 drug combinations. Nodes represent brain regions and are presented in pseudoanatomical space. Lines indicate functional relationships between nodes that are significantly altered by D1/D2 treatment relative to controls (p<0.01, n = 6–7). Solid black lines indicate gain of a positive arc CGE. Dashed black lines indicate loss of positive arc CGE. Solid red lines indicate gain of negative arc CGE. Dashed red lines indicate loss of negative CGE. (A) Effects of D2 stimulation in adolescents. (B) Effects of D2 stimulation in adults. (C) D1[Gs]/D2 combination treatment in adolescents. (D) Effects of D1[Gs]/D2 combination treatment in adults. (E) Effects of D1[Gq]/D2 combination treatment in adolescents. (F) Effects of D1[Gq]/D2 combination treatment in adults.