Senate Majority Leader Harry Reid (D-Nev.) and Minority Leader Mitch McConnell (R-Ky.) face fresh challenges as last Congress’ near-filibuster-proof Democratic majority gives way to a more evenly split chamber.

The Senate’s new partisan breakdown stands at 53-47, and a typically reserved McConnell indicated during an interview Tuesday that he expects the Senate to function much differently than it did the previous two years — to the Republicans’ benefit. Specifically, he does not expect his Conference to spend the next two years playing defense.

“Elections have consequences,” McConnell said during a conversation in his Capitol office. “Let’s assume [Senate Democrats] were able to jam something through. Do you think it would go anywhere in the House? It’s completely futile for them to continue the tactics that they used in the last Congress. To what end?”

Immediately following the Nov. 2 elections, Reid moved to put Democrats on more solid political footing in the 112th Congress and prepare for an emboldened Republican minority.

The Nevada Democrat refashioned the majority’s communications operation, tapping message guru and Conference Vice Chairman Charles Schumer (N.Y.) to run the new war room, while using the recently concluded lame-duck session to push Democratic priorities independent of what President Barack Obama wanted.

In fact, last month Reid specifically rebuffed the White House on the scheduling of votes on key legislation, and more of this is expected after a two-year period in which Senate Democrats disposed of one White House request after another. Reid expects more cooperation from Republicans as a result of the responsibility to govern that comes with their takeover of the House and strengthened ranks in the Senate.

“Sen. Reid sees the Republicans being a little bit more cooperative than in the past,” a senior Democratic Senate aide said. “The Republicans can’t just say no anymore.”

McConnell also said he believes more bipartisanship is in the offing — but for very different reasons.

Just fewer than two dozen Democrats are up for re-election in 2012, and a handful are running in conservative-leaning states and enter the election cycle potentially vulnerable. A key component of Republicans’ legislative strategy is to force votes on politically tricky issues that otherwise resonate with Republican and conservative voters.

In this manner, McConnell is hoping to go on the offensive and either damage the Democrats’ electoral prospects or cobble together a bipartisan coalition to secure passage of GOP priorities sent over from the House. Essentially, the Minority Leader is hoping to turn the tables and do some jamming of his own.

“We have 23 Democrats who are up in ’12. Many of them, I think, are listening to the American people and saying: ‘They want us to address spending, they want us to address debt — and by the way, I don’t think they like the health care bill that we passed,’” McConnell said. “I think we could have the potential of building bipartisan majorities in the Senate for things that most of my Members are for anyway.”

Former Sen. Trent Lott (R-Miss.), who served as Minority Leader and Majority Leader, said both Reid and McConnell must adjust their strategies to be successful in the months ahead. Lott said the unusual dynamic of a Republican House and Democratic Senate and White House adds a measure of unpredictability to the mix.

Lott said party unity is going to be a lot harder for Reid, and he said the former Majority Whip is going to need all of the skills he has learned over the years in leadership to hold his Conference together.

But McConnell also is going to face an added burden of leadership, Lott added. Given that House Republicans are going to send the Senate several pieces of legislation that the GOP is likely to want to send to the president, the onus will occasionally be on McConnell to find the votes to make that happen.

“They both have to review how they’re going to do business,” said Lott, who served with both Reid and McConnell. “Assuming the House is able to pass some legislation that McConnell would like to get through, he’ll have to come up with the votes.”

One consequence of the new Republican House majority and strengthened Senate minority could be fewer GOP-led filibusters.

The Republicans spent the 111th Congress pushing back against legislation sent over by a Democratic House that it deemed too liberal. Additionally, Senate Democrats knew that if they could just get a bill sent over to the House, there was a strong likelihood it would pass and make it to the president’s desk. The strong GOP majority in the House negates both dynamics.

Senate Republicans might have additional reasons for shying away from the filibuster.

“Senate Republicans are no longer the first line-stopper,” said one Republican lobbyist with relationships in the Senate. “Is it better for Mitch McConnell to force Reid to round up 51 or better to let the Democrats in tough races hide behind a filibuster? I think we will want to let the conservative Democrats vote often on tough issues.”