Researchers gave rats a choice task to see if certain brain‑active peptides could block or mimic the feeling of alcohol. The tested peptides (including TRH, its metabolite, and several others) did not change how the rats recognized alcohol, nor did they act like alcohol themselves.

Male Sprague-Dawley rats were trained to discriminate ethanol (2 g/kg, PO: EtOH) from saline (10 ml/kg, PO: SAL) in a two-bar positively reinforced operant task on a VI 15 sec schedule. After the rats reached criterion performance (greater than 90% correct responses on the appropriate lever), thyrotropin releasing hormone (pyroGlu-His-Pro-NH2: TRH), a metabolite of TRH (His-Pro diketopiperazine: HP), and a structural analog of TRH (HPCA-His-ThiaPro-NH2: OHT) were tested for their ability to antagonize the EtOH cue. These peptides were chosen for their reported ability to reverse ethanol-induced narcosis. However, at doses that did not disrupt performance, TRH, HP, and OHT did not affect the stimulus properties of ethanol at any dose tested, nor did they change the stimulus properties of saline. Naloxone and ACTH(1-10)-NH2 were also tested as ethanol antagonists of the training dose. Pretreatment with either of these compounds failed to alter ethanol-appropriate responding. In addition, (DA1a2-Met5)-enkephalin-ol, (DAla2-Met(O)5)-enkephalin-ol, substance P, delta sleep-inducing peptide, and bombesin were tested for their ability to elicit ethanol appropriate responding. The EtOH cue generalized to none of these peptides.