Behavioral responses of avoiding (AV), balancing (BA), and approaching (AP) mice in the EPM.

<p>All animals regardless the category they belonged to spent more time in the close arms, exhibiting thus the normal open arm avoidance.</p

Correlation between frequency of white choices in the A/A Y-Maze (abscissa) and contact time of object in the OF (ordinate).

<p>A positive significant correlation has showed in the scatter plot. Abbreviations: AV: avoiding animals; BA: balancing animals; AP: approaching animals.</p

Behavioral responses of avoiding (AV) and approaching (AP) mice in A/A Y-Maze and OF.

<p>On the left side, the responses of AV animals treated with URB597 (URB) or vehicle (VHL) in A/A Y-Maze (<b>A1</b>, <b>A2</b>) and OF (<b>C1–C4</b>). AV+URB animals displayed enhancement of white choices and decrease of entry latencies mainly in entering the black arm, while they were more active in exploring the environment and contacting the object in the OF than AV+VHL animals. On the right side, the responses of AP animals treated with AM251 (AM) or vehicle (VHL) in A/A Y-Maze (<b>B1</b>, <b>B2</b>) and OF (<b>D1–D4</b>). AP+AM did not change the number of white choices, decreased entry latencies in the white arm in A/A Y-Maze, while they were less active in exploring the environment and contacting the object in the OF than AP+VHL animals. Abbreviations: W: white arm; B: black arm; S1: first session; S2: second session. Asterisks indicate the significance level of the <i>post hoc</i> comparisons between groups: * <i>P</i><0.05; ** <i>P</i><0.005; *** <i>P</i><0.0005.</p

Electrophysiological effects of drugs acting on endocannabinoid system in avoiding (AV) and approaching (AP) mice.

<p>(<b>A</b>) The graph shows that treatment with URB597 was able to rescue the effect of the CB1 receptor agonist HU210 on sIPSC frequency in neurons from the AV animals. The HU210-induced inhibition of sIPSC frequency in AV+URB animals was comparable to that seen in BA animals. The treatment with the CB1 receptor antagonist AM251 fully abolished HU210 responses in AP mice. (<b>B</b>) The counterbalanced pharmacological manipulations between categories showed that in AV mice blockade of CB1 receptors with AM251 did not modify HU210 responses of GABAergic striatal neurons, while the treatment of AP animals with URB maintained the high sensitivity of striatal GABAergic synapses to HU210. Asterisks indicate the significance level of the comparisons between AV+URB <i>vs.</i> AV+VHL animals and AP+AM <i>vs.</i> AP+VHL animals: * <i>P</i><0.05.</p

Responses of striatal neurons of avoiding (AV), balancing (BA), and approaching (AP) animals.

<p>The graph shows that the sEPSC frequency reduction induced by cannabinoid CB1 receptor agonist HU210 was analogous in the AV, BA, and AP animals.</p

Behavioral responses of avoiding (AV), balancing (BA), and approaching (AP) mice in the S1 of OF.

<p>Central crossings (<b>A</b>), freezing (<b>B</b>), defecation boluses (<b>C</b>), total distance (<b>D</b>) are depicted. Asterisk indicates the significance level of the <i>post hoc</i> comparisons between groups: ** <i>P</i><0.01.</p

Responses to conflicting stimuli of adolescent mice in A/A Y-Maze.

<p>(<b>A</b>) Curves of distribution of the white and black choices of 206 animals during the sessions. (<b>B</b>) Curve of distribution of the A/A conflict index, considered as the difference (Δ) in the number of white choices between sessions. Entry latencies in the white and black arms of the entire sample of animals (<b>C</b>) and of the avoiding, balancing and approaching animals (<b>D</b>) during sessions, as well as latencies in the ten trials of S1 (<b>E</b>) in the three categories of animals are depicted. Abbreviations: W: white arm; B: black arm; S1: first session; S2: second session; AV: avoiding animals; BA: balancing animals; AP: approaching animals. In <b>C</b>, <b>D</b>, <b>E</b> and in the following figures, data are presented as means ± SEM. Asterisks indicate the significance level of the <i>post hoc</i> comparisons: in (<b>D</b>) AP <i>vs.</i> AV or BA groups: ** <i>P</i><0.01; in (<b>E</b>) AV <i>vs.</i> AP groups: * <i>P</i><0.05, *** <i>P</i><0.0005; AV <i>vs.</i> BA groups: # <i>P</i><0.05.</p

Responses of avoiding (AV), balancing (BA), and approaching (AP) mice in OF test.

<p>In S1, AP animals exhibited longer total distances (<b>A</b>) than AV and BA animals. In S2, AP mice spent more time in contacting the object (<b>D</b>), reduced total (<b>A</b>) and peripheral (<b>B</b>) distances. AV and BA animals displayed similar response patterns in almost all OF parameters (<b>A–D</b>). Abbreviations: S1: first session; S2: second session. Asterisks indicate the significance level of the <i>post hoc</i> comparisons between groups: * <i>P</i><0.05; ** <i>P</i><0.005; *** <i>P</i><0.0005.</p