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Paul Chryst isn't much of a gambler, but given the choice the first-year Pitt coach would rather go down swinging.

Unfortunately, the Panthers are doing a lot of that lately.

Pitt let No. 18 Louisville take over in the third quarter of a 45-35 loss on Saturday then squandered a late rally when a risky fourth-down pass fell incomplete and allowed the Cardinals to put it away.

Trailing by 10 with 5 minutes to play, the Panthers (2-4, 0-3 Big East) faced fourth-and-eight at the Louisville 22. A field goal would have gotten Pitt within a touchdown with plenty of time to get the ball back.

Instead, Chryst sent the offense back out on the field. Though Tino Sunseri's pass to Cam Saddler wasn't close, Chryst would make the same choice again.

"I felt like we could get it," Chryst said. "I wanted to put it in the players' hands ... I felt good putting the play call in. We didn't execute it."

Louisville running back Senorise Perry dashed 59 yards down the sideline for his fourth touchdown a few plays later as the Cardinals (6-0, 1-0) snapped a four-game slide against Pitt.

"Opening up the Big East schedule with a win is a big confidence boost for us," Louisville quarterback Teddy Bridgewater said. "Hopefully it will send a message to the rest of the Big East."

Bridgewater passed for 304 yards for the Cardinals, including a 75-yard score to DeVante Parker on the first play of the second half as Louisville continued its best start since 2006. Parker's TD came in the middle of a 24-point burst by Louisville spanning the second and third quarters that turned a seven-point deficit into a 38-21 lead.

"At any point in the game when momentum goes away, you've got to fight to get it back your way," Chryst said. "We didn't do that and that's where, during the third quarter, you saw the separation."

Sunseri passed for 287 yards and two touchdowns but Pitt (2-4, 0-3) couldn't keep pace after a solid first half in which it never trailed.

"They were making good plays and they were just doing things that I guess we weren't ready for," said Pitt running back Rushel Shell.

Louisville began the season as the overwhelming Big East favorite but some of the shine was stripped away by sluggish road wins at overmatched Florida International and Southern Mississippi coupled with the impressive starts by No. 20 Rutgers and No. 21 Cincinnati.

The Cardinals have been parked in the bottom third of the Top 25 all year despite its perfect start, leading coach Charlie Strong to play Aretha Franklin's version of "Respect" repeatedly over the last two weeks.

Following a dominant second half that came on the heels of a fiery halftime pep talk by Strong, Louisville hopes the playlist gets an upgrade.

"I'm getting pretty sick of it," center Mario Benavides said.

And the Panthers are getting pretty sick of spinning their wheels.

Pitt had dominated the Cardinals recently, winning each of the last four meetings, including a 21-14 win in Louisville last fall that helped prevent the Cardinals from securing an outright Big East title.

For about 29 minutes on Saturday, it looked as if the Panthers would extend the streak to five before the programs go their separate ways when Pitt bolts to the Atlantic Coast Conference next summer.

Playing like the team that upset Virginia Tech last month instead of the one that bumbled its way to a loss at Syracuse last week, Pitt took a 21-14 lead late in the first half behind a spectacular 7-yard touchdown pass from Sunseri to Saddler, a blocked punt by Todd Thomas that ended with the sophomore linebacker falling on it in the end zone and a 2-yard leap Shell.

When the Panthers got greedy, however, they got in trouble. Faced with a fourth-and-1 at the Louisville 42 late in the first half, Pitt opted to go for it. Shell was stuffed for a 1-yard loss and Louisville took over.

Three plays generated little and the Cardinals had fourth-and-8 at their own 45 with 22 seconds left. Rather than kick, Louisville gambled and Bridgewater delivered a pretty 27-yard completion to Parker.

The play gave Louisville enough room for John Wallace to hit a 45-yard field goal just before the gun and provide the Cardinals the kickstart they would need.

"Give credit to the Louisville defense because we did a good job and when we scored, they scored," said Pitt running back Ray Graham. "I just think coming out of the third quarter, that one play there caught us off guard."