Motivational effects of a single intra-VTA BDNF infusion in drug-nondependent rats. (A) Blockade of the dopaminergic system with neuroleptics (alpha-flupenthixol, 0.8 mg/kg) blocked the rewarding effects of morphine (10 mg/kg) in nondependent rats after a single intra-VTA BDNF (0.25 μg) infusion, but not after intra-VTA PBS infusion (*P < 0.05). The same treatment failed to block the rewarding effects of morphine in nondependent rats when BDNF was infused rostral, ventral, or lateral to the VTA because of missed cannulae placements (*P < 0.05). Error bars indicate SE of the mean. (B) Intra-VTA BDNF alone did not affect the sizes of the conditioned place preferences produced by acute morphine administration in drug-nondependent rats (*P < 0.05). (C) BDNF restored the rewarding properties of acute morphine administration in drug-nondependent TPP-lesioned rats (*P < 0.05). (D) Cresyl violet–stained coronal section showing one side of a bilateral TPP lesion and (below) a schematic of the anatomical region from which the section displayed was taken. The arrow indicates the TPP lesion area. (E) Cresyl violet–stained coronal section of a typical bilateral intra-VTA cannula placement.

Motivational and electrophysiological effects of a single intra-VTA BDNF infusion in drug-nondependent rats. (A) Blockade of the dopaminergic system with alpha-flupenthixol blocked the rewarding effects of an intra-VTA–administered GABAA receptor antagonist bicuculline (50 ng) in nondependent rats after a single intra-VTA BDNF infusion, but not after intra-VTA PBS infusion (*P < 0.05). (B and C) Single-unit extracellular recordings of VTA GABAergic neurons showing the effects of two current applications of muscimol (+50 nA) and baclofen (+50 nA) on the firing rate of representative VTA GABAergic neurons. In saline-treated rats, muscimol always decreased the firing rate of the VTA GABAergic neurons, whereas in BDNF-treated rats, muscimol enhanced the firing rate. Conversely, in both saline-treated and BDNF-treated rats, baclofen moderately decreased the firing rate of these VTA GABA neurons, as in this example.