K. T. Reyes¹, N.K. Amissah¹, S. Sawant², E. Olusanya¹, P.J. Meyer¹

Genome-wide association studies have identified teneurin-4 (Tenm4) as a potential candidate gene underlying individual variation in drug-related traits, including cue-reactivity. Teneurin-4 produces the peptide Teneurin C-terminal Associated Peptide 4 (TCAP-4), which we hypothesized would alter reward cue-reactivity as tested by Pavlovian conditioned approach (PavCA). Based on prior evidence that another TCAP (TCAP-1) crosses the blood-brain barrier, we chose intravenous administration instead of ICV. Fifty-six female Sprague Dawley rats were implanted with intravenous jugular catheters to administer TCAP-4. Rats were randomly assigned to one of four groups: 0 pmol (n=14), 300 pmol (n=14), 1000 pmol (n=14) or 3000 pmol (n=14). Rats underwent eight daily PavCA sessions. Rats received IV TCAP-4 (300, 1000, or 3000 pmol) or vehicle (0 pmol) 30 minutes before each of five PavCA sessions, followed by three sessions in which TCAP-4 was not given. The main measures in PavCA testing included lever contacts, food cup entries, lever and food cup latency, and PavCA index. Following the last PavCA session, two days of 40-minute conditioned reinforcement tests were conducted to evaluate how well the lever reinforces an instrumental response. TCAP-4 did not produce the expected reduction in cue approach (sign-tracking), although food cup entries (goal-tracking) increased significantly (p < 0.05), with the largest increases in early sessions. This suggests a shift away from lever-directed incentive salience rather than a global reduction in learning. The conditioned reinforcement test suggested TCAP-4 reduced reinforcing value of the cue. These results identify Tenm4 as a potential regulator of individual differences in cue-guided motivation.

¹Department of Psychology, University at Buffalo, Buffalo NY, ²UC James L. Winkle College of Pharmacy, Cincinnati, Ohio

Funding Support: DA060669