Chapter 4: Discussion of Results

3: PND51-60

In the Y-maze, there were no significant drug effects for either BZP- or MA- treated rats on percentage of novel arm entries or percentage of time spent in the novel arms across the three different behavioural testing periods. However, of interest is the behaviour displayed by the

BZP- (10 mg/kg) and MA (1.0 mg/kg) treated rats, who preferred to enter the novel arm at PND120 over the familiar arm and this was significantly difference from chance. Similarly, at PND200, rats treated with BZP (5 & 10 mg/kg) and all three doses of MA preferred to enter the novel arm over the familiar arm, however only the MA- treated rats (1.0 mg/kg at PND120 and all 3 doses at PND200) preferred to spend time in it. Although this would suggest they displayed decreased anxiety-like behaviour, it is more likely that once in the novel arm they froze as evidenced by decreased closed arm entries by the all the rats mentioned. This implies that they had no deficits in spatial memory as they remembered from the acquisition trail which arm had changed in brightness and were actively looking for a means of escape and once they realised there was no way out of the apparatus froze, suggestive of increased anxiety-like behaviour.

In the Light/dark emergence test, the general pattern of results were consistent over time, with all treated female rats having a shorter latency to emerge from the dark compartment,

compared to male rats, with the exception of BZP-treated rats at PND120, however this was approaching significance (P<.0781). BZP-treated rats (5 mg/kg) displayed a longer latency to emerge at PND120 and PND200, and rats treated with BZP (20 mg/kg) or all three MA doses had a longer latency to emerge from dark compartment at PND200, compared to control rats.

On the EPM, BZP- treated rats (5 mg/kg) displayed a decreased percentage of open arm entries at the 30 day wash-out period, compared to control rats, with all BZP-treated females

displaying a higher percentage of open arm entries than males. The drug x sex interactions illustrated that MA treated-females (0.5 & 1.0 mg/kg) made a higher percentage of entries and spent a longer percentage of time in the open arms of the EPM compared to male treated rats. At PND120, rats treated with BZP (10 & 20 mg/kg) or MA (2.0 mg/kg) made significantly fewer entries of the open arms and the sex x drug interaction suggests the both the male and female 2.0 mg/kg MA- treated rats made significantly fewer entries of the open arms,

compared to controls or the other MA- treated male and female rats. However, the sex x drug interaction on percentage of time spent in the open arms illustrates that only the 2.0 mg/kg male MA- treated rats had a significantly less percentage of time spent on the open arms. These results suggest that the highest dose of MA treated male rats upon entering the open arms would flee significantly faster from the aversive environment back to the safety of the closed arms, compared with 0.5 and 1.0 mg/kg male and female MA-treated rats. This reflects that the male rats treated with the highest dose of MA during PND51-60 displayed more anxiety-like behaviour on this measure at PND120. At PND200, rats treated with MA (1.0

mg/kg) made significantly more entries of the open arms than control rats. However, the sex x drug interaction illustrates that this interaction effect was due to the MA- (1.0 mg/kg) treated female rats only. Although there were no significant dose effects for treated rats on percentage of open arm time, a sex x drug interaction illustrated that male rats treated with MA (2.0mg/kg) spent significantly less percentage of time in the open arms compared to the two smaller doses of MA- treated rats and female MA- treated rats. Both BZP- and MA- treated female rats made significantly more entries of the open arms than male treated rats.

Inthe SI test, the highest BZP dose (20mg/kg) treated rats entered significantly more squares

in the OF and made more outer rears, compared to saline treated rats, conversely, the highest dose of MA (2.0 mg/kg) treated rats entered significantly fewer squares in the OF and made significantly fewer outer rears than saline controls, at the 30 day wash-out period.

Interestingly, at this first behavioural testing phase, male BZP- and MA- treated rats spent a significantly longer time in social interaction than similar treated female rats. Social interaction is proposed to measure decreased anxiety (File, 2003), however this does not appear to be consistent with the other behavioural measures and results displayed by male rats in the SI test. It is possible that the male-treated rats in this study found the novelty of the OF more aversive than interaction with another unfamiliar male rat. At PND120, BZP- treated rats (10 & 20 mg/kg) entered more squares in the OF, and made significantly more outer rears than saline- treated rats. The highest dose of BZP- (20 mg/kg) treated rats made significantly more centre rears than saline controls and BZP-treated rats (10 & 20 mg/kg) made more outer rears at PND120 than control rats. Overall, the general pattern of results is more complex than the other two adolescence periods, with MA- treated female rats displaying increased anxiety-like behaviours as the MA dose increases. And the highest doses of BZP administered to rats during PND51-60 displaying decreased emotionality, as evidenced by increased rearing

behaviours, howeverthis may be accounted for byan augmented need to scan the environment

for an escape from the aversive novel environment.

The sex effects for rats treated during PND51-60, are not as clear as observed at the other adolescent dosing periods, possibly due to a greater number of sex x dose interaction effects for the PND51-60 MA-treated rats. Both BZP- and MA- treated female rats displayed greater locomotor activity, as evidenced in the Y-maze total arm entries, EPM closed arm entries, and squares entered in the OF of the SI, compared to treated male rats, across all testing periods. There were, however significant differences for MA-treated female rats, with female rats administered MA (1.0 & 2.0 mg/kg) making fewer entries of both arms of the Y-maze

compared to male MA-treated ratsand female rats treated with 0.5 mg/kg of MA at PND120. Additionally, female rats treated with 20 mg/kg of BZP or 1.0 mg/kg of MA made significantly fewer closed arm entries on the EPM compared to male treated rats at PND200.

In document The behavioural implications of postnatal exposure to benzylpiperazhie and methamphetamine a longitudinal doserelated study in male and female rats (Page 121-125)