3,5-DHPG influences behavioral effects of baclofen in rats

The role of 3,5-DHPG, an agonist of group I metabotropic glutamate receptors (I mGluRs) in certain behavioral effects of baclofen, an agonist of GABA-B receptor, was assessed. Baclofen, given intraperitoneally (ip) at the dose of 0.25 mg/kg, enhanced the number of crossings and bar approaches in the open field and was ineffective in the passive avoidance tests, and it prolonged time spent in closed arms and shortened time spent in open arms, reduced number of entries into open arms in the elevated "plus" maze, measuring anxiety. 3,5-DHPG given intracerebroventricularly (icv) alone at doses of 0.01, 0.1 and 1.0 nmole did not change locomotor activity in the open field test, except bar approaches: when 3,5-DHPG was given at the dose of 0.01 nmole it enhanced the activity of rats. At doses of 0.01 and 1.0 nmole it improved, but at the dose of 0.1 nmole it significantly impaired retrieval in the passive avoidance situation. All used doses of 3,5-DHPG did not influence the time spent in closed or open arms and the number of entries into open or closed arms in the elevated "plus" maze. 3,5-DHPG, given at the doses of 0.01, 0.1 and 1.0 nmole 10 min after baclofen significantly changed the effect of baclofen decreasing crossings and rearings in the open field, while 3,5-DHPG used at the doses of 0.01 and 1.0 nmole in rats pretreated with baclofen reduced bar approaches. Rats which received baclofen and, 10 min later, 3,5-DHPG at doses of 0.1 and 1.0 nmole, showed significantly improved retrieval in the passive avoidance response. The effect of 3,5-DHPG and baclofen were changed, i.e. 3,5-DHPG and baclofen can cooperate in retrieval process. Coadministration of baclofen and 3,5-DHPG at the dose of 1.0 nmole reduced time spent in the open arms in comparison with baclofen, i.e. this dose of 3,5-DHPG changed the effect of baclofen evaluated in the "plus" maze. Summary, the activation of I mGluR by 3,5-DHPG modulates GABA-B neurotransmission stimulated by baclofen, which is reflected by changing behavioral activity of rats.