N-Methyl-d-aspartate (NMDA)–mediated long-term potentiation and conditioned place avoidance are elicited by the activation of estrogen receptor-β and G protein–coupled estrogen receptor-1 but not estrogen receptor-α. (A–C) The estrogen receptor-β agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; A) and the G protein–coupled estrogen receptor-1 agonist (±)-1-[(3aR*,4S*,9bS*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl]-ethanone (G1; B) induces the long-term potentiation of NMDA-mediated excitatory postsynaptic currents (NMDA–long-term potentiation) in pyramidal neurons in rostral anterior cingulate cortex slices. n = 7 and 10. Vehicle (0.1% dimethyl sulfoxide) and the estrogen receptor-α agonist 4,4´,4´´-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT; C) did not affect NMDA receptor–mediated excitatory postsynaptic currents; n = 7 and 11. (D) Exposure to 17β-estradiol (E2) after PPT application elicited NMDA-mediated long-term potentiation; n = 8. (E) Schematic of the protocol for experiments F to H. (F–H) Microinjections of the estrogen receptor-β agonist DPN (0.02 ng/μl, 0.5 μl/hemisphere) or the G protein–coupled estrogen receptor-1 agonist G1 (0.2 μg/μl, 0.5 μl/hemisphere) directly into the rostral anterior cingulate cortex–induced conditioned place avoidance. **P < 0.001 versus the preconditioning test (two-tailed paired t test); ^##P < 0.01 versus vehicle (10% dimethyl sulfoxide; one-way ANOVA followed by post hoc Dunnett’s test); n = 8, 8, and 8.