The hole board search task (HBST) measures long-term and short-term memory, operationally defined as reference memory and working memory. The HBST is an open-field spatial learning test. Previously, we have shown that desglycinamide(Arg8) vasopressin (DGAVP) modulated reference memory, working memory, spatial sequence memory, and learning in the HBST in a dose-dependent manner (Vawter MP, Van Ree JM. Effects of des-glycinamide-sup-9-(arginine-sup-8) vasopressin upon spatial memory in the hole-board search task. Psychobiology 1995; 23: 45-51). To examine the potential active site of the DGAVP molecule, the fragment of the vasopressin amino acid sequence, [pGlu4,Cyt6]AVP-(4-8) (AVP-(4-8)), was administered 1 h prior to training in the HBST. Three groups received either 0, 0.3 microgram, or 1 microgram AVP-(4-8). A repeated measures MANOVA showed the AVP-(4-8) pretreatment factor to be significant (P = 0.048) on the reference memory measure, but not the working memory or learning measures. Interactions between peptide x sessions for reference memory (P = 0.015), working memory (P = 0.003) and learning (P = 0.010) indicated differences in improvement over sessions between placebo- and peptide-treated groups. Post hoc comparisons revealed that the AVP-(4-8) fragment in a dose of 0.3 microgram increased reference memory on the fourth, fifth and sixth acquisition sessions compared with placebo or 1 microgram AVP-(4-8) pretreated groups. Working memory and errors were significantly lowered by 0.3 microgram AVP-(4-8) on the first acquisition session when compared with placebo pretreatment. Thus, AVP-(4-8) improves long-term and short-term memory scores in the HBST, similar to previous results with DGAVP. However, AVP-(4-8) appears twice as potent than DGAVP in improving long-term memory scores in the HBST. The data suggest that the memory modulating property of DGAVP is contained within the amino acid sequence of the AVP-(4-8) peptide.
